The only cathelicidin the human body makes, with thousands of papers on what it does inside us, one drug programme that reached Phase 2b and missed, and a gray market that injects it for reasons no study has examined.

Summary

  • LL-37 is a 37-amino-acid antimicrobial peptide cleaved from the precursor protein hCAP18. It is produced by neutrophils and epithelial cells, kills bacteria by disrupting their membranes, and signals to immune cells, blood vessels and skin.1

  • It is also a driver of disease. LL-37 is a T-cell autoantigen in psoriasis and promotes the inflammation of rosacea; its overexpression is part of both conditions.23

  • In cancer it cuts both ways: tumour-promoting in ovarian, lung, breast, prostate, pancreatic and skin cancers and melanoma; tumour-suppressing in colon, gastric and some blood cancers.4

  • The one serious drug programme, topical LL-37 for venous leg ulcers, produced a positive 34-patient Phase 2a in 2014 and a 148-patient Phase 2b in 2021 that "did not identify any significant improvement in healing" against placebo.56

  • A small Indonesian trial of LL-37 cream on diabetic foot ulcers reported faster granulation; a Phase 1 of intratumoral LL-37 in melanoma enrolled four people.78

  • No study has ever given LL-37 systemically to a human being. Every trial applied it to a wound or injected it into a tumour.

  • The FDA placed it in Category 2 of its compounding policy in 2023, citing immunogenicity and nonclinical findings of "detrimental effects on male reproduction and that this drug can be protumorigenic in some tissues." It was not among the peptides considered by the advisory committee in July 2026.9

  • A targeted PubMed search returns 2,546 records and ClinicalTrials.gov lists 20 studies. Nearly all of the first are basic immunology, and nearly all of the second measure LL-37 levels rather than give it.

The Most Common Error About This Compound

Reading the size of the literature as evidence for the product. LL-37 is one of the best-studied molecules in innate immunity, and the ONPEPS grade rule, which counts publications and late-stage trials, places it at B on that basis. Almost none of that literature concerns giving LL-37 to a person. The therapeutic record is two wound-healing trials, one of which was negative, and the studies that would justify injecting it for "immune support" do not exist.

Identity

What Is LL-37?

Cathelicidins are a family of antimicrobial peptides found across mammals. Humans have exactly one, encoded by the CAMP gene and produced as an 18-kilodalton precursor, hCAP18, which is stored in neutrophil granules and secreted by skin, gut and airway epithelium. Cleavage releases the active 37-residue peptide, named for its two leading leucines. It forms an amphipathic helix that inserts into bacterial membranes, and at lower concentrations it acts as a signalling molecule: chemoattracting immune cells, promoting blood vessel growth and wound closure, modulating inflammation, and binding and neutralising bacterial endotoxin.1 Its production in skin and macrophages is induced by vitamin D, which is why the two are so often studied together.

Why Is It Not Simply "Good"?

Because the same molecule that defends the body also attacks it. In psoriasis, LL-37 forms complexes with self-DNA that activate plasmacytoid dendritic cells, and it is itself recognised by T cells as an autoantigen in a large fraction of patients.2 In rosacea, abnormally high protease activity in the skin generates LL-37 fragments that drive the inflammation and vascular changes of the disease; injecting those fragments into mouse skin reproduces it.3

A person adding LL-37 to their own supply is adding a molecule that, in the wrong tissue at the wrong concentration, is a disease mechanism.

Evidence Base

What Is the Literature Actually About?

Mechanism and measurement. The great majority of the 2,546 papers study what LL-37 does in cells, in animals, or in patients with a condition, by measuring how much of it they have. The 20 registered trials are mostly of that last kind: LL-37 levels in gingival fluid, in periodontitis, in type 1 diabetes, in tuberculosis patients given vitamin D.10 That work is why the peptide is well understood. It is not evidence that giving it does anything.

Venous Leg Ulcers

The one programme that tested LL-37 as a drug, run by the Swedish company Promore Pharma under the name ropocamptide.

The 2014 first-in-human trial enrolled 34 people with hard-to-heal venous leg ulcers, with a three-week placebo run-in, four weeks of twice-weekly topical LL-37 at three concentrations or placebo, and four weeks of follow-up. Healing rate constants were about six-fold higher than placebo at 0.5 mg/mL and three-fold at 1.6 mg/mL; the highest dose, 3.2 mg/mL, did no better than placebo. There were no safety concerns.5

The Phase 2b, HEAL LL-37, enrolled 148 people at the two lower doses or placebo alongside compression therapy. Efficacy analysis on the full population "did not identify any significant improvement in healing in patients treated with LL-37 as compared with the placebo." A post hoc analysis found improvement in the subgroup with wounds of at least 10 cm², which the authors said "exigently" warranted a further, adequately powered study.6 That study has not been run.

The pattern, a strong small trial followed by a negative larger one with a rescued subgroup, is the most common shape in drug development, and it is the shape of this compound's therapeutic record.

Diabetic Foot Ulcers

A randomised, double-blind trial in Jakarta applied LL-37 cream or placebo twice weekly for four weeks to diabetic foot ulcers with mild infection. The granulation index increased more in the LL-37 group at every time point; the inflammatory cytokines and bacterial counts the study also measured did not differ.7 The registered enrolment was 40.11 It is a positive signal on a surrogate outcome in a small trial.

Melanoma

A Phase 1/2 trial at MD Anderson injected LL-37 directly into melanoma lesions to test whether it could provoke an anti-tumour immune response. It enrolled four people and completed in 2020; the registered results report the number reaching an optimal biological dose and are not interpretable as efficacy.8 It is worth remembering that LL-37 is tumour-promoting in melanoma in the laboratory; the trial was testing whether a large local dose could flip that.4

What Is It Sold For?

"Immune support," chronic infection, Lyme disease, biofilm, gut health and long COVID, as a subcutaneous injection. No study has given LL-37 systemically to a human. A 2024 review of cathelicidins in skin therapeutics notes that "many peptide-based therapies have failed in clinical trials due to unclear efficacy and safety concerns," and that bacterial resistance to cathelicidins, once thought impossible, has emerged.12

Safety

What Is Known?

Topical LL-37 on wounds was well tolerated in both leg ulcer trials, with no local or systemic safety concerns.56 That is the whole of the human safety record, and it concerns a cream on a wound.

What the FDA Said

The Category 2 entry for cathelicidin LL-37 is one of the few on the list to name specific nonclinical harms: compounded LL-37 "may pose risk for immunogenicity for certain routes of administration," the FDA "lacks sufficient safety-related information," and "nonclinical research findings suggest detrimental effects on male reproduction and that this drug can be protumorigenic in some tissues."9

The tumour point is not speculative. LL-37 promotes growth, migration or invasion in ovarian, lung, breast, prostate, pancreatic and skin cancer cells and melanoma, through receptors that differ by tissue.4 A person with an undiagnosed cancer of one of those types who injects LL-37 systemically is doing something no animal study has been designed to test and every mechanistic study suggests is unwise.

What Is Unknown

Everything about systemic administration in humans: dose, half-life, distribution, whether injected LL-37 reaches any tissue intact, whether it provokes the autoimmune responses it participates in, and what it does to a tumour nobody knows is there. LL-37 is also cytotoxic to human cells at higher concentrations, a property that limits its therapeutic window even topically and that the 2014 trial's failure at the highest dose may reflect.5

Regulatory Status

Is It Approved Anywhere?

No. LL-37 has no marketing authorisation for any indication in any jurisdiction, and the ropocamptide programme has not advanced since 2021. It is not named on the WADA Prohibited List; as an unapproved substance it may fall under S0, and a tested athlete should ask their anti-doping organisation.

Where Does It Stand on Compounding?

In September 2023 the FDA placed cathelicidin LL-37 in Category 2 of its interim compounding policy. As of April 2026 it appears among substances nominated but withdrawn, with the original safety text unchanged.9 It was not among the peptides the Pharmacy Compounding Advisory Committee considered in July 2026, and no vote concerns it.13 It is not on the 503A bulks list, and no pharmacy in the United States has a lawful basis on which to compound it.

Related ONPEPS Coverage

What Would Change This Page

The adequately powered large-wound trial the HEAL LL-37 authors called for, which would settle whether topical LL-37 has a place in venous ulcer care.6 Any study of systemic LL-37 in a human, which would be the first. Neither is registered.

References

  1. Vandamme D, Landuyt B, Luyten W, Schoofs L. A comprehensive summary of LL-37, the factotum human cathelicidin peptide. Cell Immunol. 2012;280(1):22-35. Paywalled. pubmed.ncbi.nlm.nih.gov/23246832

  2. Lande R, Botti E, Jandus C, Dojcinovic D, Fanelli G, Conrad C, et al. The antimicrobial peptide LL37 is a T-cell autoantigen in psoriasis. Nat Commun. 2014;5:5621. Open access. pubmed.ncbi.nlm.nih.gov/25470744

  3. Yamasaki K, Di Nardo A, Bardan A, Murakami M, Ohtake T, Coda A, et al. Increased serine protease activity and cathelicidin promotes skin inflammation in rosacea. Nat Med. 2007;13(8):975-980. Open access. pubmed.ncbi.nlm.nih.gov/17676051

  4. Chen X, Zou X, Qi G, Tang Y, Guo Y, Si J, et al. Roles and mechanisms of human cathelicidin LL-37 in cancer. Cell Physiol Biochem. 2018;47(3):1060-1073. Open access. pubmed.ncbi.nlm.nih.gov/29843147

  5. Grönberg A, Mahlapuu M, Ståhle M, Whately-Smith C, Rollman O. Treatment with LL-37 is safe and effective in enhancing healing of hard-to-heal venous leg ulcers: a randomized, placebo-controlled clinical trial. Wound Repair Regen. 2014;22(5):613-621. Paywalled. pubmed.ncbi.nlm.nih.gov/25041740

  6. Mahlapuu M, Sidorowicz A, Mikosinski J, Krzyżanowski M, Orleanski J, Twardowska-Saucha K, et al. Evaluation of LL-37 in healing of hard-to-heal venous leg ulcers: a multicentric prospective randomized placebo-controlled clinical trial. Wound Repair Regen. 2021;29(6):938-950. Open access. pubmed.ncbi.nlm.nih.gov/34687253

  7. Miranda E, Bramono K, Yunir E, Reksodiputro MH, Suwarsa O, Rengganis I, et al. Efficacy of LL-37 cream in enhancing healing of diabetic foot ulcer: a randomized double-blind controlled trial. Arch Dermatol Res. 2023;315(9):2623-2633. Paywalled. pubmed.ncbi.nlm.nih.gov/37480520

  8. ClinicalTrials.gov. NCT02225366. Intratumoral Injections of LL37 for Melanoma. Sponsor M.D. Anderson Cancer Center. Phase 1/2, 4 participants, completed November 2020, results posted. Record retrieved 16 September 2026. clinicaltrials.gov/study/NCT02225366

  9. US Food and Drug Administration. Category 2 of the Bulk Substances Nominated Under Sections 503A or 503B of the Federal Food, Drug, and Cosmetic Act. Entry for cathelicidin LL-37. Content current as of 22 April 2026. fda.gov

  10. ClinicalTrials.gov. Studies listing LL-37 as an intervention. Registry search; most entries measure LL-37 levels rather than administer it. clinicaltrials.gov

  11. ClinicalTrials.gov. NCT04098562. Efficacy of LL-37 Cream on Bacteria Colonization, Inflammation Response and Healing Rate of Diabetic Foot Ulcers. Sponsor Fakultas Kedokteran Universitas Indonesia. Phase 2, 40 participants estimated. Record retrieved 16 September 2026. clinicaltrials.gov/study/NCT04098562

  12. Dzurová L, Holásková E, Pospíšilová H, Schneider Rauber G, Frébortová J. Cathelicidins: opportunities and challenges in skin therapeutics and clinical translation. Antibiotics (Basel). 2024;14(1):1. Open access. pubmed.ncbi.nlm.nih.gov/39858288

  13. US Food and Drug Administration. July 23-24, 2026: Meeting of the Pharmacy Compounding Advisory Committee. Agenda listing the seven substances considered; LL-37 is not among them. Docket FDA-2025-N-6895. fda.gov

Not Medical Advice

LL-37 is not approved for human use in any jurisdiction, has never been given systemically to a person in a study, and promotes several common cancers in laboratory work. Consult a qualified healthcare provider before acting on anything here.

Evidence counts on the library index retrieved 23 July 2026; the grade those counts produce reflects the size of the immunology literature rather than therapeutic evidence. Literature and regulatory sources verified 16 September 2026. Re-verify before relying on any regulatory statement here.