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LL-37

Tier 2 · Preclinical
Also known as Cathelicidin · hCAP-18

The strongest evidence present is Tier 1, including the HEAL LL-37 phase IIb double-blind, randomized, placebo-controlled trial in 148 patients with venous leg ulcers5 and several Tier-1 human observational reviews and mechanistic studies1,2,3,4,6,7,8. Importantly, controlled human evidence is limited to topical wound-healing studies; the pivotal phase IIb trial was negative in its full population with benefit only in a post hoc large-wound subgroup. Broader claims (antiviral, antifungal, antitumor, antibiofilm, gut-barrier, cardiovascular) rest largely on in vitro, animal, theoretical, or expert-opinion sources, and no controlled trials of injected/systemic LL-37 exist.

Half-life
Not recorded
Routes
Topical (gel/cream, used in human trials) · Subcutaneous (community protocols only, not trial-validated)
Goals
healing · immune support
Cost / mg
Not recorded

How it works

LL-37 is described by sources as the only human cathelicidin — a 37-amino-acid, positively charged peptide cut from a precursor protein called hCAP-18. Because it carries a positive charge, it is drawn to the negatively charged surfaces of bacteria, where a Tier-1 review reports it punches holes in and permeabilizes microbial membranes, killing many bacteria (gram-positive and gram-negative), some fungi, and some viruses. Beyond killing microbes directly, sources describe it as an immune-signaling molecule: it binds and neutralizes bacterial endotoxin, recruits immune cells, and can dissolve bacterial biofilms and drive neutrophils to release DNA nets. Reviews stress that it has both anti- and pro-inflammatory effects and can be both protective and harmful depending on context — it is also cytotoxic to human cells at higher concentrations and has been implicated in diseases such as psoriasis and lupus. In wound healing, sources report it promotes new blood-vessel growth and skin-cell migration.

Overview

Overview

LL-37 (also called cathelicidin or hCAP-18) is described across sources as the only known human cathelicidin — a 37-amino-acid cationic peptide cleaved from the precursor protein hCAP-181,10. Tier-3 vendor guides list its physical properties as 37 amino acids, ~4,493 Da, a +6 net charge at physiological pH, an isoelectric point of ~10.6, and encoding on chromosome 3p21.3(vendor claim). Note that CAS numbers differ between sources: one lists 154947-66-7 while another lists 137265-46-4.

Biology and Origin

A Tier-3 guide and Tier-2 review10 describe the CAMP gene encoding a ~170-amino-acid preprotein that becomes the 18 kDa hCAP-18 proform, from which proteinase 3 releases the mature LL-37 peptide upon neutrophil degranulation. Sources report LL-37 is stored in neutrophil granules and produced by macrophages, dendritic cells, NK cells, epithelial cells, and keratinocytes, with concentrations rising at sites of infection, inflammation, and wound healing. A Tier-1 study and Tier-1 review report that 1,25-dihydroxyvitamin D upregulates CAMP gene expression (about a 170-fold mRNA increase in THP-1 monocytes3), though a Tier-1 review cautions that only limited evidence shows vitamin D consistently increases biologically active LL-37 peptide7.

Reported Activities

A Tier-1 review reports LL-37 is active against gram-positive and gram-negative bacteria and some viruses, modulates innate immunity by binding/inactivating bacterial endotoxins, promotes chemotaxis of immune cells, and mediates Ca2+ import2. The same review describes direct bactericidal action via bacterial cell-wall permeabilization, biofilm dissolution, and promotion of neutrophil extracellular traps (NETs)2. In vitro reviews report broad activity — one against 38 bacteria, 16 fungi, and 16 viruses9, and another finding all 43 tested clinical bacterial strains susceptible with natural resistance uncommon10. Tier-2 reviews report LL-37 can prevent biofilm establishment by a wide range of pathogens12 and shows in vitro promise against drug-resistant organisms including MRSA, VRE, and resistant Klebsiella9.

A Tier-1 clinical trial report notes endogenous LL-37 is abundant in acute wounds but absent in chronic wounds, suggesting a role in natural wound healing5, and animal/ex vivo models report local LL-37 stimulates healing of chronic wounds5. Sources also describe angiogenic and keratinocyte-migration effects.

Human Clinical Evidence

The strongest human evidence is topical. The HEAL LL-37 phase IIb double-blind, randomized, placebo-controlled study evaluated topical LL-37 with compression therapy in 148 patients with hard-to-heal venous leg ulcers, using LL-37 at 0.5 or 1.6 mg/mL versus placebo5. The trial reported that the full-population efficacy analysis found no significant healing improvement versus placebo, while a post hoc analysis showed statistically significant improvement in the subgroup with large wounds (≥10 cm2)5. 2014); readers should weigh these subgroup figures against the negative primary result. A Tier-3 guide states the only controlled human trials of administered LL-37 are topical wound-healing studies in venous leg and diabetic foot ulcers, with no published placebo-controlled trials of systemic subcutaneous, intramuscular, or intravenous LL-37 for any indication(vendor claim). A Tier-3 dosing site notes LL-37 is investigational as ropocamptide(vendor claim).

Context-Dependent and Investigational Roles

Sources emphasize LL-37 has both anti- and pro-inflammatory effects1,2. A Tier-3 vendor guide and Tier-2 review describe LL-37/self-nucleic-acid complexes activating plasmacytoid dendritic cells via TLR9/7/8 to drive type I interferon as a documented pathogenic mechanism in psoriasis, systemic lupus erythematosus, psoriatic arthritis, and atherosclerosis15. A Tier-2 study reports LL-37 localizes in atherosclerotic plaques and induces endothelial-to-mesenchymal transition via Akt/NF-κB, theorizing a role in atherosclerosis pathogenesis11. A Tier-3 review reports contradictory tumor effects — overexpression promoting ovarian, lung, and breast cancers but suppressing colon and gastric cancer20. A Tier-1 review reports a prominent and complex role in inflammatory bowel disease6. Broader online claims that LL-37 treats infections, Lyme disease, long COVID, wounds, immune dysfunction, or anti-aging are, per a Tier-3 guide, not established by strong human clinical trials.

Regulatory Status

Sources agree LL-37 is not FDA-approved for any indication6,18. Regulatory descriptions of the 503A bulks list conflict: one Tier-3 source states it is not on the §503A bulks list, while another states it is on the FDA's 503A Category 1 bulk drug substances list and available only as a compounded prescription through licensed 503A compounding pharmacies.

A third Tier-3 source that cites FDA regulatory documents helps settle this conflict: as of its May 2026 verification, LL-37 is not on the current §503A bulks list. FDA documents describe LL-37 as having been placed in Category 2 — bulk substances that raise significant safety concerns — and then removed only because the nomination was withdrawn, with FDA intending to consult its Pharmacy Compounding Advisory Committee before the end of February 2027 about possible inclusion. The framing that LL-37 sits on a "503A Category 1" list and is therefore routinely compoundable is a single-source claim that the FDA-based descriptions do not support; the weight of the sources is that LL-37 is not currently a listed compoundable bulk substance and its status is unresolved pending further FDA review.

What the research shows

191 findings extracted from the 21 sources cited below, strongest evidence first within each group. Every one links to the source it came from.

What human studies found

Based on 3 human trial findings, 12 human study findings, 2 animal findings, 4 in vitro findings and 18 expert opinion findings.

  • human trialHEAL LL-37 was a phase IIb double-blind, randomized, placebo-controlled study to evaluate the efficacy and safety of LL-37 for topical administration in combination with compression therapy in 148 patients with hard-to-heal venous leg ulcers5

  • human trialEfficacy analysis performed on the full study population did not identify any significant improvement in healing in patients treated with LL-37 compared with placebo5

  • human trialPost hoc analysis revealed statistically significant improvement with LL-37 treatment in several interrelated healing parameters in the subgroup of patients with large target wounds (wound area of at least 10 cm2 at randomization)5

  • human studyLL-37 shows activity towards both gram-positive and gram-negative bacteria2

  • human studyLL-37 is active against some types of viruses2

  • human studyIn psoriatic lesions very high concentrations (300 µM) of LL-37 are detected2

  • human studyIn periodontitis, gingival crevicular fluid contains about 1 µM LL-372

  • human studyLL-37 primarily kills already infected and weakened cells2

Show 31 more findings

  • human studyLL-37 plays a prominent and complex role in inflammatory bowel disease (IBD)6

  • human studyOverexpression of LL-37 has been implicated in inflamed and noninflamed colon mucosa in patients with ulcerative colitis6

  • human studyLL-37 expression was not changed in inflamed or noninflamed colon or ileal mucosa in patients with Crohn's disease6

  • human studyCathelicidins have protective effects in both ulcerative colitis and Crohn's disease in animal models and human patients6

  • human studyLL-37 peptide is a potent killer of different microorganisms8

  • human studyLL-37 is localized in atherosclerotic plaques11

  • human studyThe rate of LL-37/hCAP-18 positive cells ranged from 60 (ITP) to 0.5% (M5)17

  • animalLocal administration of LL-37 has been shown to stimulate healing of chronic wounds in experimental animals and in an ex vivo model of human acute wounds5

  • animalLL-37 is able to prevent biofilm establishment by different bacterial pathogens such as Acinetobacter baumannii, Aggregatibacter actinomycetemcomitans, Bacteroides fragilis, Burkholderia thailandensis, Cutibacterium acnes, Escherichia coli, Francisella tularensis, Helicobacter pylori, Klebsiella pneumoniae, Pseudomonas aeruginosa, Staphylococcus aureus, and Streptococcus pyogenes12

  • in vitroLL-37 shows broad antimicrobial activity, effective against 38 bacteria, 16 fungi, and 16 viruses9

  • in vitroAll tested clinical isolates were susceptible to LL-37 under the experimental conditions, confirming its broad-spectrum antimicrobial activity10

  • in vitroNatural resistance to LL-37 is uncommon among bacterial pathogens10

  • in vitroRecombinant LL-37 exhibits consistent antimicrobial activity across diverse clinical isolates10

  • expert opinionLL-37 has potent antimicrobial properties1

  • expert opinionLL-37 has antiviral properties1

  • expert opinionLL-37 has antifungal properties1

  • expert opinionLL-37 has antiparasitic properties1

  • expert opinionLL-37 has antitumor properties1

  • expert opinionOnly limited evidence is presented showing that 1,25D3 consistently increases the amount of biologically active LL-37 peptide7

  • expert opinionLL-37 has been proposed as a marker of inflammation severity and treatment outcome14

  • expert opinionLL37 has demonstrated anti-inflammatory, wound healing, and immunomodulatory effects18

  • expert opinionLL37 is effective against antibiotic resistant pathogens like methicillin-resistant Staphylococcus aureus (MRSA)18

  • expert opinionLL37 accelerates healing in chronic wounds, diabetic ulcers, and burns18

  • expert opinionLL37 modulates inflammation in inflammatory bowel disease (IBD), psoriasis, and rheumatoid arthritis18

  • expert opinionLL37 demonstrates antiviral activity against respiratory viruses including influenza and SARS-CoV-218

  • expert opinionLL37 has been investigated for its ability to suppress tumor growth by modulating the tumor microenvironment18

  • expert opinionLL37 is effective in breaking down biofilms in chronic infections such as dental and sinus infections18

  • expert opinionLL-37 shows great potential to be developed as a drug with clinical use19

  • expert opinionLL-37 can have two different and contradictory effects--promotion or inhibition of tumor growth20

  • expert opinionOverexpression of LL-37 was found to promote development and progression of ovarian, lung and breast cancers20

  • expert opinionOverexpression of LL-37 was found to suppress tumorigenesis in colon and gastric cancer20

How it works

Based on 3 human trial findings, 20 human study findings, 1 animal finding, 23 in vitro findings, 56 expert opinion findings and 12 theoretical findings.

  • human trialThe human cathelicidin LL-37 shows activity against microorganisms, but it is also cytotoxic to host cells3

  • human trialThe CAMP gene codes for the LL-37 precursor hCAP18 which is processed extracellularly to active LL-373

  • human trialVitamin D stimulates CAMP gene activity3

  • human studyLL-37 modulates innate immunity through binding and inactivation of bacterial endotoxins2

  • human studyLL-37 promotes chemotaxis of immune cells2

  • human studyLL-37 interacts with plasma membrane receptors and mediates import of Ca2+2

  • human studyLL-37 has both anti- and pro-inflammatory effects2

  • human studyLL-37 has a direct bactericidal effect through permeabilization of the bacterial cell wall2

Show 107 more findings

  • human studyLL-37 can dissolve bacterial biofilms2

  • human studyLL-37 promotes formation of neutrophil extracellular traps (NETs)2

  • human studyEndogenous LL-37 was abundantly present in acute wounds, but was absent in chronic wounds, suggested a role of this peptide in natural wound healing5

  • human study1,25D3 up-regulates expression of the human antimicrobial peptide hCAP-18/LL-37 gene7

  • human studyThe hCAP-18/LL-37 gene seems to be an important transcriptional target for 1,25D37

  • human study1,25D3-induced stimulation of hCAP-18/LL-37 gene expression represents an important pathway for 1,25D3-evoked regulation of the innate immune response7

  • human studyLL-37 is the only known member of the cathelicidin family of peptides expressed in humans8

  • human studyLL-37 is a multifunctional host defense molecule essential for normal immune responses to infection and tissue injury8

  • human studyLL-37 can prevent immunostimulatory effects of bacterial wall molecules such as lipopolysaccharide and can therefore protect against lethal endotoxemia8

  • human studyLL-37 has chemoattractant function8

  • human studyLL-37 inhibits neutrophil apoptosis8

  • human studyLL-37 stimulates angiogenesis, tissue regeneration, and cytokine release (e.g. IL-8)8

  • human studyCellular production of LL-37 is affected by bacterial products, host cytokines, availability of oxygen, and sun exposure through the activation of CAP-18 gene expression by vitamin D(3)8

  • human studyAt infection sites, the function of LL-37 can be inhibited by charge-driven interactions with DNA and F-actin released from dead neutrophils and other cells lysed as the result of inflammation8

  • human studyLow translation efficiency of LL-37/hCAP-18 in some leukemia cells might be one of the reasons that leukemia patients were susceptible to infection17

  • animalCathelicidins, a family of HDPs, are produced by diverse animal species such as mammals, fish, birds, amphibians, and reptiles to protect them against pathogen infections13

  • in vitroA physiological concentration of vitamin D (50 nM) enhances CAMP mRNA levels by about 170 times in human THP-1 monocyte cells3

  • in vitroStimulation with 50 nM vitamin D increases hCAP18/LL-37 protein contents 3-4 times in THP-1 cell lysates3

  • in vitroTreatment with the proteasome inhibitor MG132 enhances hCAP18/LL-37 levels, suggesting that turnover of hCAP18/LL-37 protein is regulated by the proteasome3

  • in vitroLL-37 disrupts multiple microbial pathways, reducing resistance in bacteria, fungi, and viruses9

  • in vitroLL-37 shows structural versatility, with mono-, di-, and tetrameric forms supporting function and stability9

  • in vitroLL-37 effectively combats over 38 bacteria, 16 fungi, and 16 viruses through various mechanisms, including membrane rupture, targeting, and biofilm suppression9

  • in vitroMechanisms involve cell wall destruction, membrane permeabilization, oxidative stress, cell cycle arrest, adhesion prevention, gene modification, and disruption of viral envelopes, entry, and replication9

  • in vitroLL-37 is a multifaceted peptide with antimicrobial and immunomodulatory actions11

  • in vitroLL-37 decreased EC markers but increased mesenchymal cell markers in human umbilical vein ECs11

  • in vitroLL-37 decreased the vascular network formation of cells but increased cell migration11

  • in vitroLL-37-induced EndMT was inhibited by Akt and nuclear factor-kappa B (NF-κB) inhibitors, suggesting that LL-37 induces EndMT by activating Akt and NF-κB11

  • in vitroLL-37 has broad-spectrum antimicrobial activity and immunomodulatory properties12

  • in vitroInhibition of bacterial adhesion is a major mechanism responsible for antibiofilm properties of LL-3712

  • in vitroDownregulation of biofilm-associated genes is a major mechanism responsible for antibiofilm properties of LL-3712

  • in vitroSuppression of quorum-sensing pathways is a major mechanism responsible for antibiofilm properties of LL-3712

  • in vitroDegradation of biofilm matrix is a major mechanism responsible for antibiofilm properties of LL-3712

  • in vitroEradication of biofilm-residing cells is a major mechanism responsible for antibiofilm properties of LL-3712

  • in vitroLL-37 peptide is released from human cathelicidin (hCAP-18)14

  • in vitroLL-37 can directly perform antimicrobial action after insertion into surface structures of microorganisms14

  • in vitroLL-37 has immunomodulatory function as an agonist of different cell membrane receptors14

  • in vitroLL-37/hCAP-18 expression at mRNA level was detected and varied among six of nine cell lines17

  • in vitroThe level of Raji cells was about eight folds higher than that of Ramos cells17

  • in vitroOnly two cell lines, J6-1 and U937, expressed protein products17

  • expert opinionLL-37 has potent antimicrobial, antiviral, antifungal, antiparasitic, and antitumor properties1

  • expert opinionTruncated and retro-analogs of LL-37 preserve or improve biological activity while exhibiting reduced toxicity and increased proteolytic resistance1

  • expert opinionAntimicrobial peptides serve as key effectors of the innate immune system offering protection against Gram-positive and Gram-negative bacteria, fungi, and viruses1

  • expert opinionLL-37 is the only human cathelicidin1

  • expert opinionLL-37 has broad-spectrum antimicrobial activity1

  • expert opinionLL-37 has immunomodulatory functions1

  • expert opinionLL-37 is a proteolytic fragment of cathelicidin4

  • expert opinionLL-37 fulfills the roles of a defensin by inserting into the membranes of bacterial pathogens4

  • expert opinionLL-37 functions as alarmin in stimulating chemotaxis of innate immune cells4

  • expert opinionLL-37 alters the structure and efficacy of various cytokines4

  • expert opinionLL-37 has direct effect on neutrophils and the release of extracellular traps (NETs)4

  • expert opinionNETs function as mediators of immune defense against pathogens4

  • expert opinionNETs are important contributors to chronic disease and tissue pathogenesis4

  • expert opinionLL-37 has structural flexibility and ability to adapt to distinct microenvironments and interacting counterparts4

  • expert opinionLL-37 is a 37-meric peptide derived by proteolytic cleavage from the 18-kDa human cathelicidin antimicrobial protein (hCAP18)5

  • expert opinionLL-37 is the only member of the cathelicidin family of host defense peptides expressed in humans6

  • expert opinionLL-37 plays a crucial role in host defense against pathogen invasion6

  • expert opinionLL-37 regulates anti-inflammation, antitumorigenesis, and tissue repair functions6

  • expert opinionLL-37 is primarily produced by phagocytic leukocytes and epithelial cells6

  • expert opinionLL-37 mediates a wide range of biological responses6

  • expert opinionLL-37 is usually expressed at high concentrations by various white blood cells10

  • expert opinionLL-37 plays an important role in the innate immune defense against bacterial and viral infections10

  • expert opinionLL-37 effectively disrupts bacterial membranes10

  • expert opinionLL-37 is derived through proteolysis of its precursor, the human cationic antimicrobial peptide (hCAP18)10

  • expert opinionhCAP18 is considered an 18 kDa propeptide, which consists of signal peptide, a conserved cathelin domain, and the antimicrobial peptide LL-37 residing in the C-terminal domain10

  • expert opinionLL-37 is the only member of cathelicidin family synthetized in humans10

  • expert opinionCathelicidins are expressed at high concentrations in neutrophil-specific granules, which can be released upon neutrophil activation10

  • expert opinionLL-37 (hCAP-18) is the only identified human cathelicidin antimicrobial peptide16

  • expert opinionCathelicidins have antimicrobial effects16

  • expert opinionCathelicidins have lipopolysaccharide-neutralizing effects16

  • expert opinionCathelicidins profoundly affect both innate and adaptive immunity16

  • expert opinionLL-37 has a role in lung physiology and defense16

  • expert opinionLL-37/hCAP-18 is an important part of host defense17

  • expert opinionLL37 is a naturally occurring antimicrobial peptide derived from cathelicidin, an immune defense molecule produced by epithelial cells, immune cells, and keratinocytes18

  • expert opinionLL37 is the only human cathelicidin identified so far18

  • expert opinionLL37 plays a vital role in the innate immune system by combating bacterial, viral, and fungal pathogens18

  • expert opinionLL37 disrupts microbial membranes leading to cell lysis and death18

  • expert opinionLL37 targets gram positive and gram negative bacteria, fungi, and viruses18

  • expert opinionLL37 regulates immune responses by modulating cytokine production, enhancing macrophage activity, and promoting anti-inflammatory pathways18

  • expert opinionLL37 stimulates angiogenesis, epithelialization, and tissue repair by attracting immune cells to injury sites and promoting collagen synthesis18

  • expert opinionLL37 penetrates and breaks down biofilms that shield pathogens from antibiotics and the immune system18

  • expert opinionLL-37 is the sole human cathelicidin19

  • expert opinionLL-37 has broad spectrum antibiotic properties19

  • expert opinionLL-37 has potent chemotactic properties19

  • expert opinionLL-37 has potent immunomodulatory properties19

  • expert opinionLL-37 is a C-terminal peptide proteolytically released from 18 kDa human cathelicidin protein (hCAP18)20

  • expert opinionChronic infections, inflammation, tissue injury and tissue regeneration are all linked with neoplastic growth, and involve LL-37 antibacterial and immunomodulatory functions20

  • expert opinionThe mechanisms are tissue-specific, complex, and depend mostly on the ability of LL-37 to act as a ligand for different membrane receptors whose expression varies on different cancer cells20

  • expert opinionCathelicidins are antimicrobial peptides produced by humans and animals in response to various pathogenic microbes21

  • expert opinionCathelicidins act as a primary defense against bacteria and other pathogens in the case of inflammation21

  • expert opinionThey are able to kill bacteria and fungi, inhibit and destroy bacterial biofilms21

  • expert opinionCathelicidins possess antiviral and antiparasitic properties21

  • expert opinionThey can play a role in angiogenesis, wound healing, and the regulation of apoptosis21

  • expert opinionLL-37 has emerged as a novel modulator of tumor growth and metastasis in carcinogenesis of various types of cancers21

  • expert opinionLL-37 acts as an anti- and pro- inflammatory factor21

  • expert opinionCathelicidins are able to directly and selectively destroy membranes of various microbes and cancer cells, but they do not attack normal cells21

  • theoreticalHost defense peptides (HDPs) are naturally occurring polypeptide sequences that are active against bacteria, fungi, viruses, and other parasites13

  • theoreticalHost defense peptides may stimulate immunomodulatory responses13

  • theoreticalCathelicidins have variable C-terminal domains responsible for their antimicrobial and immunomodulatory activities and a highly conserved N-terminal pre-pro region homologous to cathelin13

  • theoreticalCathelicidins are major components of innate immunity13

  • theoreticalLL-37 fragments (SK-24, IV-20, FK-13 and LL-37) play a role in the immunity response13

  • theoreticalLL-37 fragments may be responsible for interaction between these peptides and receptors in humans13

  • theoreticalAntimicrobial peptides (AMPs) such as β-defensin, S100, and cathelicidin are secreted from cells and activate the innate immune system through various mechanisms to induce inflammation, thus participating in the pathogenesis of psoriasis15

  • theoreticalAntimicrobial peptides enhance the binding of damage-associated molecular patterns such as self-DNA and self-RNA to their receptors and promote the secretion of interferon from activated plasmacytoid dendritic cells and keratinocytes to promote inflammation in psoriasis15

  • theoreticalNeutrophil extracellular traps (NETs), complexes of self-DNA and proteins including LL-37 released from neutrophils in psoriatic skin, induce Th1715

  • theoreticalActivated myeloid dendritic cells secrete a mass of inflammatory cytokines such as IL-12 and IL-23 in psoriasis, which is indispensable for the proliferation and survival of T cells that produce IL-1715

  • theoreticalAMPs enhance the production of some of Th17 and Th1 cytokines and modulate receptors and cellular signaling in psoriasis15

  • theoreticalInflammation induced by DAMPs, including self-DNA and RNA released due to microinjuries or scratches, and the enhanced recognition of DAMPs by AMPs, may be involved in the mechanism underlying the Köbner phenomenon in psoriasis15

Dosing

Based on 1 human trial finding.

  • human trialStudy had three arms consisting of two groups treated with LL-37 at concentrations of 0.5 or 1.6 mg/mL, and a placebo cohort5

How the body handles it

Based on 2 in vitro findings and 1 expert opinion finding.

  • in vitroThe hCAP18/LL-37 concentration in vitamin D-stimulated THP-1 cells corresponds to 1.04 μM LL-373

  • in vitroMIC concentrations obtained for recombinant LL-37 were comparable to those reported for chemically synthesized and commercially available LL-3710

  • expert opinionNanoscale delivery systems facilitate targeted delivery, prolong peptide half-life, and mitigate cytotoxic effects of LL-371

Safety and side effects

Based on 1 human trial finding, 1 human study finding, 2 in vitro findings and 7 expert opinion findings.

  • human trialThe study drug was well tolerated and safe in both dose strengths5

  • human studyLL-37 is cytotoxic to many different human cell types, particularly infected cells, when administered at final concentrations of 1–10 µM2

  • in vitroSynthetic LL-37, at 1.04 μM concentration, reduces viability of human osteoblast-like MG63 cells3

  • in vitroTHP-1 cells are less sensitive to LL-37-induced cytotoxicity than human osteoblast-like MG63 cells3

  • expert opinionClinical application of LL-37 is hindered by low proteolytic stability, cytotoxicity, and high production costs1

  • expert opinionClinical application of LL-37 is hindered by several limitations1

  • expert opinionClinical application faces challenges like degradation and toxicity9

  • expert opinionIssues such as proteolytic sensitivity and potential high-concentration toxicity must be addressed9

Show 3 more findings

  • expert opinionAMPs have low or not yet observed bacterial resistance10

  • expert opinionThere are still many questions to be answered regarding LL-37 efficacy and safety in vivo12

  • expert opinionLL37 is not FDA approved18

What people use it for

Based on 1 human study finding, 1 in vitro finding, 16 expert opinion findings and 1 theoretical finding.

  • human studySeveral diseases in human are characterized by impairment in the function of LL-37/hCAP-18 peptide17

  • in vitroLL-37 shows therapeutic promise against drug-resistant infections like MRSA, VRE, and resistant Klebsiella9

  • expert opinionLL-37-based analogs represent promising candidates for the development of next-generation antimicrobial and immunomodulatory therapies1

  • expert opinionLL-37 promotes wound healing10

  • expert opinionOral LL-37 expression is an important factor in maintaining physiological microbiota in oral homeostasis14

  • expert opinionLL-37 is involved in the development of oral dysbiosis14

  • expert opinionLL-37 is involved in the development of infectious diseases including viral, bacterial, and fungal infections14

  • expert opinionLL-37 is involved in the development of autoimmune diseases and oral carcinomas14

Show 11 more findings

  • expert opinionAntimicrobial peptides including LL-37 are being evaluated as therapeutic drugs in oral mucositis, cystic fibrosis, and septic shock16

  • expert opinionLL37 is useful in managing chronic sinusitis, urinary tract infections, and respiratory infections18

  • expert opinionLL-37 shows potential as a therapeutic agent in immunological systems19

  • expert opinionLL-37 shows potential as a therapeutic agent in respiratory systems19

  • expert opinionLL-37 shows potential as a therapeutic agent in gastrointestinal systems19

  • expert opinionLL-37 shows potential as a therapeutic agent in skin systems19

  • expert opinionLL-37 may be a therapeutic agent against a variety of bacterial and viral diseases, cancers, and hard-to-heal wounds21

  • expert opinionLL-37 could be applied in pharmacotherapy due to its activity spectrum21

  • expert opinionCathelicidin peptides could serve as a template for the development of modern anti-microbial and anti-viral drugs21

  • expert opinionLL-37 is an excellent candidate to develop into therapeutics for infected wounds21

  • theoreticalLL-37 may play a role in the pathogenesis of atherosclerosis as an EndMT inducer11

Other findings

Based on 3 expert opinion findings.

  • expert opinionLL-37 is the only human cathelicidin1

  • expert opinionFuture studies should focus on creating stable analogs, optimizing delivery mechanisms, and exploring synergistic combinations with existing antibiotics9

  • expert opinionHuman cathelicidin LL-37 is one of the best studied antimicrobial peptides10

Points of contention

Where the evidence is unsettled, thin, or says less than the popular claim — worth knowing before you draw conclusions.

Limited evidence

No controlled human trials of injected/systemic LL-37 exist; only topical wound trials.

Multiple sources state the only controlled human trials of administered LL-37 are topical wound-healing studies in venous leg ulcers and diabetic foot ulcers, with no published placebo-controlled trials of subcutaneous, intramuscular, or intravenous LL-37 for any indication. Community subcutaneous protocols (100-250 mcg/day, up to 500 mcg/day) are extrapolations from preclinical work, not trial-validated.

Contested

The pivotal phase IIb wound trial was negative overall; benefit came only from a post hoc subgroup.

The HEAL LL-37 trial in 148 patients found no significant healing improvement versus placebo in the full population; a statistically significant benefit appeared only in a post hoc analysis of patients with large wounds (≥10 cm2). Tier-3 guides emphasize the subgroup finding (28.1% vs 8.1% closure; 'six times faster') without foregrounding the negative primary result.

Contested

LL-37 is both protective and pathogenic depending on context.

Sources describe LL-37 as having both anti- and pro-inflammatory effects. While antimicrobial and wound-healing roles are highlighted, LL-37/self-nucleic-acid complexes are a documented pathogenic mechanism in psoriasis, SLE, psoriatic arthritis, and atherosclerosis, and LL-37 can both promote (ovarian, lung, breast) and suppress (colon, gastric) tumor growth.

Limited evidence

Cytotoxicity to human cells is a recognized limitation.

LL-37 is cytotoxic to many human cell types at 1–10 µM (reducing osteoblast-like MG63 cell viability at 1.04 µM), and clinical application is hindered by low proteolytic stability, cytotoxicity, and high production costs. The FDA also notes nonclinical findings of possible detrimental effects on male reproduction and protumorigenic effects.

Contested

CAS numbers differ between sources.

One tier-3 source lists CAS number 154947-66-7, while another tier-3 source lists CAS number 137265-46-4 for LL-37.

Single source

Conflicting CAMP/vitamin D 'consistency' of active peptide increase.

A tier-1 review notes only limited evidence shows 1,25D3 consistently increases biologically active LL-37 peptide, even though vitamin D robustly upregulates CAMP gene expression (about 170-fold mRNA increase in THP-1 cells per one study).

Limited evidence

Many broad efficacy claims rest on in vitro, animal, or expert-opinion sources, not human trials.

Claims of antiviral (SARS-CoV-2, influenza), antifungal, antitumor, antibiofilm, gut-barrier, and cardiovascular effects come largely from in vitro, theoretical, or expert-opinion tiers; one tier-3 source explicitly states online claims that LL-37 treats infections, Lyme disease, long COVID, wounds, immune dysfunction, or anti-aging are not established by strong human clinical trials.

Using it with other compounds

Check a stack
  • PidotimodComplementary

    No documented conflict

    Both modulate Toll-like receptor signaling and support innate immunity, but pidotimod primarily drives dendritic-cell maturation and adaptive (Th1/antibody) responses while LL-37 provides direct antimicrobial and TLR-modulating actions. This gives coverage across innate and adaptive immune defense.

    Tier 4Theoretical — not established

    Shares innate immune · anti inflammatory · antimicrobial

  • TB-500Complementary

    May be complementary

    Both promote wound healing, new blood-vessel growth (VEGF), and reduced inflammation, but through distinct mechanisms — LL-37 drives keratinocyte migration and angiogenesis via EGFR/FPR2, while TB-500 regulates actin/cytoskeletal dynamics and cell migration. This makes them a strong complementary tissue-repair pairing.

    Tier 4Theoretical — not established

    Shares tissue repair · angiogenesis · anti inflammatory · VEGF upregulation

  • ThymulinComplementary

    No documented conflict

    Thymulin normalizes T-cell balance and dampens excess pro-inflammatory cytokines via NF-κB/p38 modulation, while LL-37 provides antimicrobial and TLR/FPR2-based innate immune actions. Their different immune targets can complement each other in immune support.

    Tier 4Theoretical — not established

    Shares innate immune · anti inflammatory

  • SemaxComplementary

    No documented conflict

    Both support angiogenesis, tissue repair, and anti-inflammatory signaling, though Semax is oriented toward neuroprotection via BDNF/NGF-TrkB pathways and LL-37 toward peripheral wound healing via VEGF/EGFR. Overlap is modest and context-dependent rather than a targeted combination.

    Tier 4Theoretical — not established

    Shares tissue repair · angiogenesis · anti inflammatory

  • TeduglutideComplementary

    No documented conflict

    Both support repair of epithelial/mucosal surfaces by different means: teduglutide promotes intestinal epithelial proliferation, while LL-37 drives keratinocyte/epithelial migration, wound closure and antimicrobial defense at mucosal barriers. They can reinforce barrier healing from separate pathways, though LL-37 can be cytotoxic at higher concentrations, so this is more speculative.

    Tier 4Theoretical — not established

    Shares tissue repair

  • VilonComplementary

    Worth caution

    LL-37 is a human cathelicidin providing frontline antimicrobial and innate-immune signaling; Vilon supports adaptive/T-cell immunity via gene reactivation. They cover different arms of immunity, so they are complementary rather than redundant, though LL-37's context-dependent pro-inflammatory effects warrant monitoring.

    Tier 4Theoretical — not established

    Shares innate immune · anti inflammatory

  • Thymosin Alpha-1Complementary

    No documented conflict

    LL-37 is a direct-acting human cathelicidin that physically kills microbes and neutralizes endotoxin, while Thymosin Alpha-1 works one level up by training and coordinating immune cells. The two attack infection through genuinely different mechanisms (direct antimicrobial vs. immune orchestration) that converge on host defense, making them potentially complementary.

    Tier 4Theoretical — not established

    Shares innate immune · anti inflammatory · antimicrobial

  • GHK-CuComplementary

    May be complementary

    GHK-Cu stimulates collagen/elastin synthesis, angiogenesis and antioxidant defenses while suppressing NF-κB, and LL-37 contributes antimicrobial defense plus angiogenic and epithelializing wound-healing effects. Their distinct mechanisms both support skin remodeling and tissue repair, making them a reasonable complementary combination for wound/skin contexts.

    Tier 4Theoretical — not established
  • BPC-157Complementary

    Worth caution

    Both promote angiogenesis and wound epithelialization, but LL-37 adds broad-spectrum antimicrobial and endotoxin-neutralizing activity that BPC-157 lacks. In a contaminated or infected wound context the two are complementary — LL-37 clears microbes/biofilm while BPC-157 drives vascular and connective-tissue repair. Note LL-37 has context-dependent pro-inflammatory effects, so monitoring is reasonable.

    Tier 4Theoretical — not established
  • Alpha-MSHComplementary

    Worth caution

    Both peptides fight microbes and modulate inflammation, but by different routes: alpha-MSH works through melanocortin receptors and NF-κB suppression, while LL-37 is a cationic cathelicidin that directly disrupts microbial membranes and signals through TLR/FPR2 pathways. Their distinct mechanisms converge on innate defense and tissue protection, so they are conceptually complementary rather than redundant.

    Tier 4Theoretical — not established

    Shares anti inflammatory · antimicrobial

  • ElafinComplementary

    May be complementary

    Both are human host-defense molecules but hit different targets: LL-37 is a cathelicidin that directly punctures microbial membranes, while elafin blocks the destructive enzymes (elastase, proteinase 3) that neutrophils release. Together they cover both direct killing and protection of the tissue from friendly-fire enzyme damage, converging on mucosal defense and repair.

    Tier 3Largely anecdotal — commonly discussed

    Shares innate immune · antimicrobial · anti inflammatory · tissue repair

  • KPVComplementary

    Worth caution

    Both have reported antimicrobial and immune-modulating activity but by different means: LL-37 is a cathelicidin that directly disrupts microbial membranes and neutralises endotoxin, while KPV calms the downstream inflammatory response via NF-κB. Together they cover microbial killing plus inflammation control, though LL-37 can be pro-inflammatory and cytotoxic at higher concentrations, so this is a nuanced pairing.

    Tier 4Theoretical — not established

    Shares innate immune · anti inflammatory

  • HumaninSame mechanism

    Worth caution

    Both LL-37 and humanin act on the formyl peptide receptor FPR2 and share anti-inflammatory, cytoprotective signaling. Because they engage the same receptor, combining them is more likely to be redundant (competing for the same target) than additive, so it makes more sense to choose one FPR2-directed agent rather than stack the two.

    Tier 4Theoretical — not established

    Shares anti inflammatory

  • ImunofanComplementary

    No documented conflict

    Imunofan bidirectionally normalizes immune function, boosts phagocytosis/NK activity and antioxidant defenses, and supports tissue repair, while LL-37 adds direct antimicrobial and TLR-based innate actions. Different mechanisms converging on immune balance and repair.

    Tier 4Theoretical — not established

    Shares innate immune · anti inflammatory · tissue repair

  • GLOWComplementary

    Worth caution

    LL-37 is a cathelicidin that promotes angiogenesis, keratinocyte migration and wound healing via VEGF/EGFR, overlapping with GLOW's repair and angiogenic goals through a distinct innate-immune mechanism. It can complement wound-healing objectives, but note LL-37 is cytotoxic at higher concentrations and has mixed pro-/anti-inflammatory behavior, so dosing restraint is warranted.

    Tier 4Theoretical — not established

    Shares tissue repair · angiogenesis · anti inflammatory · VEGF upregulation

  • LactoferrinComplementary

    May be complementary

    Both are frontline innate-immune defence peptides but attack microbes by different routes: LL-37 is a cationic peptide that punches holes in bacterial membranes, while lactoferrin starves microbes of iron and also binds their surfaces. Because the mechanisms differ, they can broaden antimicrobial coverage and both help calm inflammation — a classic complementary innate-immunity pairing seen naturally in neutrophils and mucosal fluids.

    Tier 3Largely anecdotal — commonly discussed

    Shares antimicrobial · innate immune · anti inflammatory

Safety and side effects

Safety and Side Effects

Cytotoxicity. A Tier-1 review reports LL-37 is cytotoxic to many human cell types — particularly infected and weakened cells — at final concentrations of 1–10 µM, and describes it as primarily killing already infected and weakened cells2. A Tier-1 study reports synthetic LL-37 at 1.04 µM reduces viability of human osteoblast-like MG63 cells, with THP-1 monocytes less sensitive than MG63 cells3. Tier-1 and Tier-2 reviews list cytotoxicity, low proteolytic stability, degradation, potential high-concentration toxicity, and high production costs as limitations to clinical application1,4,8,9.

Concentration context. A Tier-1 review reports very high concentrations (~300 µM) are detected in psoriatic lesions, while gingival crevicular fluid in periodontitis contains about 1 µM2. A Tier-3 dosing site notes higher doses are linked in the literature to stronger inflammatory and mast-cell effects(vendor claim).

Pro-inflammatory / autoimmune mechanism. A Tier-3 vendor guide and Tier-2 review describe LL-37 forming complexes with self-DNA and self-RNA released from damaged cells that activate plasmacytoid dendritic cells through TLR9, TLR7, and TLR8, driving type I interferon production — described as a documented pathogenic mechanism in psoriasis, systemic lupus erythematosus, psoriatic arthritis, and atherosclerosis15.

Regulatory safety notes. A Tier-3 guide states the FDA notes that compounded LL-37 may pose immunogenicity risk for certain routes and raises peptide-related impurity/characterization concerns, and reports nonclinical findings suggesting detrimental effects on male reproduction and protumorigenic effects in some tissues(vendor claim). A Tier-3 review reports tissue-dependent, contradictory tumor effects (promoting ovarian/lung/breast, suppressing colon/gastric)20.

Trial tolerability. In the HEAL LL-37 phase IIb trial, the topical study drug was reported to be well tolerated and safe at both dose strengths (0.5 and 1.6 mg/mL)5.

Overall caveat. No controlled human trials of injected or systemic LL-37 exist; safety data outside topical wound use are absent, and community subcutaneous protocols are extrapolations from preclinical work rather than trial-validated.

Reconstitution and handling

Dosing

No dose has been established for this compound. No regulatory label exists for LL-37 — sources agree it is not FDA-approved for any indication. The figures below are what sources report, not guidance.

What human trials actually used (topical only)

  • The HEAL LL-37 phase IIb randomized, placebo-controlled trial applied LL-37 as a gel to the venous leg ulcer surface, at tested concentrations of 0.5 or 1.6 mg/mL versus placebo5. A Tier-3 dosing site reports gel was applied twice a week, an earlier first-in-man study tested 3.2 mg/mL, and that the lowest concentration (0.5 mg/mL) produced the best healing rate, 1.6 mg/mL was effective but less so, and 3.2 mg/mL was not carried forward(vendor claim).
  • A Tier-3 dosing site emphasizes that human trials delivered LL-37 as a gel onto a leg ulcer — not as an injection — and that no published human trial has tested subcutaneous LL-37(vendor claim).

Community (non-trial) subcutaneous protocols

  • A Tier-3 dosing site reports a community-derived daily subcutaneous protocol — explicitly not trial-validated — clustering around 100–250 mcg per day, with some advanced write-ups up to 500 mcg per day, usually once daily, often 5 days on with 2 days off, for a 2–4 week block(vendor claim).
  • A Tier-3 vendor guide states these community subcutaneous protocols are extrapolations from preclinical work and are not validated by controlled trials(vendor claim). The same source notes higher doses are linked in the literature to stronger inflammatory and mast-cell effects.

Preparation notes

The claims provided do not specify a reconstitution diluent volume or resulting concentration for research vials. Note that LL-37 is described as having low proteolytic stability1, and a Tier-3 guide states it is available only as a compounded prescription through licensed providers and 503A compounding pharmacies; its 503A bulks-list status is described inconsistently across sources (one source vs one source).

Sources

Ordered by evidence quality — the strongest first.

  1. Antimicrobial Peptides of the Cathelicidin Family: Focus on LL-37 and Its Modifications(opens in a new tab)
    Tier 1Web · pmc.ncbi.nlm.nih.gov
  2. Human antimicrobial/host defense peptide LL-37 may prevent the spread of a local infection through multiple mechanisms: an update | Inflammation Research | Springer Nature Link(opens in a new tab)
    Tier 1Web · link.springer.com · 2025
  3. Vitamin D triggers hCAP18/LL-37 production: Implications for LL-37-induced human osteoblast cytotoxicity.(opens in a new tab)
    Tier 1PubMed · pubmed.ncbi.nlm.nih.gov · 2024
  4. LL-37, a Multi-Faceted Amphipathic Peptide Involved in NETosis.(opens in a new tab)
    Tier 1PubMed · pubmed.ncbi.nlm.nih.gov · 2022
  5. Evaluation of LL‐37 in healing of hard‐to‐heal venous leg ulcers: A multicentric prospective randomized placebo‐controlled clinical trial(opens in a new tab)
    Tier 1Web · doi.org · 2021
  6. The Roles of Cathelicidin LL-37 in Inflammatory Bowel Disease.(opens in a new tab)
    Tier 1PubMed · pubmed.ncbi.nlm.nih.gov · 2016
  7. Vitamin D3 modulates the innate immune response through regulation of the hCAP-18/LL-37 gene expression and cytokine production.(opens in a new tab)
    Tier 1PubMed · pubmed.ncbi.nlm.nih.gov · 2016
  8. Cathelicidin LL-37: a multitask antimicrobial peptide.(opens in a new tab)
    Tier 1PubMed · pubmed.ncbi.nlm.nih.gov · 2010
  9. Decoding LL-37: Structure and antimicrobial mechanisms against microbial threats(opens in a new tab)
    Tier 2Web · sciencedirect.com
  10. The Potential of Human Recombinant Cathelicidin LL-37 in the Treatment of Infections | International Journal of Peptide Research and Therapeutics | Springer Nature Link(opens in a new tab)
    Tier 2Web · link.springer.com · 2025
  11. Human cathelicidin peptide LL-37 induces endothelial-to-mesenchymal transition.(opens in a new tab)
    Tier 2PubMed · pubmed.ncbi.nlm.nih.gov · 2025
  12. Antibiofilm properties of cathelicidin LL-37: an in-depth review.(opens in a new tab)
    Tier 2PubMed · pubmed.ncbi.nlm.nih.gov · 2023
  13. The LL-37 domain: A clue to cathelicidin immunomodulatory response?(opens in a new tab)
    Tier 2PubMed · pubmed.ncbi.nlm.nih.gov · 2023
  14. Cathelicidin LL-37 in Health and Diseases of the Oral Cavity.(opens in a new tab)
    Tier 2PubMed · pubmed.ncbi.nlm.nih.gov · 2022
  15. Psoriasis and Antimicrobial Peptides.(opens in a new tab)
    Tier 2PubMed · pubmed.ncbi.nlm.nih.gov · 2020
  16. Pulmonary defense and the human cathelicidin hCAP-18/LL-37.(opens in a new tab)
    Tier 2PubMed · pubmed.ncbi.nlm.nih.gov · 2005
  17. Expression of LL-37/hCAP-18 gene in human leukemia cells.(opens in a new tab)
    Tier 2PubMed · pubmed.ncbi.nlm.nih.gov · 2003
  18. LL37: Revolutionizing Antimicrobial Therapy for Infections, Wound Healing, and Immunity(opens in a new tab)
    Tier 3Web · youtube.com
  19. LL-37: Cathelicidin-related antimicrobial peptide with pleiotropic activity.(opens in a new tab)
    Tier 3PubMed · pubmed.ncbi.nlm.nih.gov · 2016
  20. The Role of Cathelicidin LL-37 in Cancer Development.(opens in a new tab)
    Tier 3PubMed · pubmed.ncbi.nlm.nih.gov · 2016
  21. Unique features of human cathelicidin LL-37.(opens in a new tab)
    Tier 3PubMed · pubmed.ncbi.nlm.nih.gov · 2015

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