Peptides & growth hormone

LL-37

Updated · 21 sources · Editorial policy

LL-37 is the only cathelicidin antimicrobial peptide made by humans. It is a 37-amino-acid fragment cut from a larger protein called hCAP18, and it is part of the innate immune system in white blood cells, skin and other barrier tissues. Besides killing bacteria in the lab, it influences wound repair, blood-vessel growth and inflammation.

A synthetic copy of LL-37 has been tested as a topical treatment for chronic leg and foot ulcers, and once as an injection into melanoma skin metastases. No LL-37 product is approved as a medicine, and the largest randomized trial (148 patients with venous leg ulcers) missed its primary endpoint. No human study has tested LL-37 injected under the skin for recovery, injury repair or body composition.

This page summarizes what the clinical trials, laboratory research and regulators report. It is for education only and is not medical advice.

Property Detail
Class Human host-defense (antimicrobial) peptide, cathelicidin family
Origin C-terminal fragment of hCAP18, encoded by the CAMP gene
Size 37 amino acids; C₂₀₅H₃₄₀N₆₀O₅₃, molecular weight ≈4493 (PubChem)
Approval status Not approved; studied as an investigational drug (non-proprietary name ropocamptide)
Routes studied in humans Topical on ulcers; intratumoral injection in one small melanoma study
Concentrations or doses in trials 0.5–3.2 mg/mL solution on ulcers; 0.5 mg/g cream; 250–500 µg per tumor weekly
Half-life Not established; no published human pharmacokinetic study found
FDA compounding status Formerly in category 2 (may present significant safety risks); nomination withdrawn
WADA status Not named; non-approved substances fall under S0 (prohibited at all times)

What it is

LL-37 was first predicted in 1995 from a human bone-marrow gene library and named FALL-39 after its first four residues. The gene was found to be active mainly in bone marrow and testis (Agerberth et al., PNAS 1995). A year later, the same group showed that the mature peptide released from granulocytes is two residues shorter and begins with two leucines, hence the name LL-37 (Coffelt et al., PNAS 2009). They also concluded that this gene is the only cathelicidin gene in the human genome (Gudmundsson et al., Eur J Biochem 1996).

The precursor, hCAP18, is stored inside neutrophil granules. It is cut into active LL-37 only after it is released from the cell, by the enzyme proteinase 3 (Sørensen et al., Blood 2001). The peptide has no cysteine bridges, unlike the defensins, and part of it is predicted to fold into an amphipathic helix, a coil with a water-loving face and a fat-loving face (Agerberth et al., PNAS 1995). PubChem lists the formula and a molecular weight of about 4493 (PubChem CID 16198951).

Regulation by vitamin D

The CAMP gene is switched on directly by the active form of vitamin D. Its promoter carries a vitamin D response element, and 1,25-dihydroxyvitamin D3 raised CAMP expression in human keratinocytes, monocytes and neutrophils in cell culture (Wang et al., J Immunol 2004). This response element is conserved in primates but absent in mouse, rat and dog genomes (Gombart et al., FASEB J 2005). Rodent studies of vitamin D and cathelicidin therefore do not map directly onto humans. See Vitamin D3 for the vitamin itself.

Roles beyond killing bacteria

Finding Model Source
hCAP18 rises in skin after wounding, peaking at 48 h; it is low or absent at the edges of chronic ulcers Human skin biopsies Heilborn et al., J Invest Dermatol 2003
Antibodies against LL-37 blocked re-epithelialization (skin closing over a wound) Organ-cultured human skin Heilborn et al., J Invest Dermatol 2003
LL-37 triggered new blood-vessel growth via the receptor FPRL1 Endothelial cells, chick embryo membrane, rabbit hind-limb ischemia Koczulla et al., J Clin Invest 2003
LL-37 binds the body’s own DNA and turns it into a trigger for interferon release in psoriasis Human immune cells Lande et al., Nature 2007
Rosacea skin contains abnormally high cathelicidin, and the rosacea-type fragments caused skin inflammation Human skin; mice Yamasaki et al., Nat Med 2007
Patients with severe congenital neutropenia (morbus Kostmann) lacked LL-37 and had severe periodontal disease, except one with near-normal LL-37 after bone-marrow transplant 6 patients, 22 controls Pütsep et al., Lancet 2002

These findings show that LL-37 is a signaling molecule as well as an antibiotic. They also show that more LL-37 is not always better: high levels are linked to inflammatory skin disease.

How it behaves in the body

No published study reports the absorption, blood levels or half-life of synthetic LL-37 given to people by any route. The trials below applied it topically or injected it into tumors and did not report systemic pharmacokinetics.

One laboratory study found that human plasma blocks LL-37’s antibacterial activity. The peptide was not rapidly broken down in plasma; instead it bound to apolipoprotein A-I, a plasma protein that appears to act as a scavenger (Wang et al., J Biol Chem 1998). This is in vitro data and does not establish a half-life.

Because no human pharmacokinetic study could be found, this page gives no half-life figure for LL-37.

Regulatory status

  • No approval. LL-37 has been developed as an investigational drug for venous leg ulcers. The 2021 phase IIb paper notes that the developer, Promore Pharma, used the non-proprietary name ropocamptide (Mahlapuu et al., Wound Repair Regen 2021).
  • FDA compounding list. FDA placed cathelicidin LL-37 in category 2 of its interim compounding policy, the group of bulk substances that may present significant safety risks. The nomination was later withdrawn, and FDA’s page still lists its concerns: possible immunogenicity (an immune reaction against the peptide), peptide impurities, too little human safety data, and nonclinical findings of harm to male reproduction and of tumor-promoting effects in some tissues (FDA, 2026). BPC-157 is listed in the same section.
  • Sport. LL-37 is not named on the WADA list. Section S0 prohibits at all times any pharmacological substance not covered elsewhere on the list that has no current approval by a health authority for human therapeutic use (WADA 2026 Prohibited List).

What the research shows

All controlled human data come from local use on chronic wounds. There are no trials of LL-37 for muscle injury, tendon repair, recovery from training or body composition.

Venous leg ulcers: first trial (phase I/II)

The first-in-human trial enrolled 34 people with hard-to-heal venous leg ulcers. After 3 weeks on placebo, they were randomized to LL-37 solution at 0.5, 1.6 or 3.2 mg/mL or placebo, applied twice weekly for 4 weeks (Grönberg et al., Wound Repair Regen 2014):

Arm Healing rate vs placebo Mean ulcer area reduction
0.5 mg/mL ≈6× higher (p = 0.003) 68%
1.6 mg/mL ≈3× higher (p = 0.088, not significant) 50%
3.2 mg/mL No difference from placebo No improvement reported

The highest concentration did not work, which suggests the effect does not rise with dose. No local or systemic safety concerns were reported.

Venous leg ulcers: larger trial (phase IIb, HEAL LL-37)

The follow-up trial randomized 149 patients in Poland and Sweden (148 treated) to LL-37 at 0.5 or 1.6 mg/mL or placebo, applied twice weekly for 13 weeks on top of compression therapy (Mahlapuu et al., Wound Repair Regen 2021). In the full analysis set:

Outcome 0.5 mg/mL (n = 46) 1.6 mg/mL (n = 48) Placebo (n = 50)
Confirmed complete closure 26.5% 24.7% 25.3%
Healing rate per day 0.0261 0.0112 0.0204
Ulcers at least 50% smaller 56.4% 35.0% 46.2%
Mean wound area reduction 35.6% 4.0% 51.7%

None of these differences was statistically significant, so the trial failed its primary endpoint. A post hoc analysis (one decided after seeing the data) of ulcers of 10 cm² or more found closure in 28.1% on 0.5 mg/mL vs 8.1% on placebo (p = 0.0458, one-sided). In smaller ulcers, placebo did numerically better. Post hoc subgroup results like this generate hypotheses and need a new trial to confirm. Three authors were employees of the developer.

Diabetic foot ulcers

A double-blind trial in Jakarta randomized 25 people with diabetic foot ulcers (mostly uninfected or mildly infected) to a 0.5 mg/g LL-37 cream (n = 13) or placebo cream (n = 12), applied twice weekly for 4 weeks (Miranda et al., Arch Dermatol Res 2023):

Day Granulation index gain, LL-37 Granulation index gain, placebo p
7 0.41 0.16 0.031
14 0.60 0.27 0.009
21 0.64 0.30 0.006
28 0.64 0.36 0.037

The granulation index is the share of the wound bed covered by new healing tissue. LL-37 did not lower the inflammatory markers IL-1α or TNF-α, and it did not significantly reduce bacterial counts. The trial was small and lasted only 4 weeks.

Melanoma skin metastases

MD Anderson ran a phase I/II study of LL-37 injected weekly into cutaneous melanoma metastases, starting at 250 µg per tumor for up to 8 weeks. Only 4 people enrolled and 3 were reported in the results, at 250 or 500 µg per tumor (ClinicalTrials.gov NCT02225366). The study is too small to judge efficacy.

Oral engineered bacteria for COVID-19

One open-label trial in 238 inpatients with COVID-19 tested a Lactococcus lactis strain engineered to produce LL-37, taken by mouth, and reported faster viral RNA clearance when started early (Zhao et al., J Med Virol 2023). This was a live bacterial product, not the synthetic peptide, and the trial was not blinded.

Side effects and risks

What the trials reported

  • Leg ulcer trials. In the phase IIb trial, 43% of patients reported at least one adverse event, with similar numbers across arms (20, 24 and 20 patients). Six events in 4 patients were judged possibly related to the study product (wound infection, dermatitis, leg swelling, and one deep phlebitis in the placebo group). Serious events occurred in 11 patients (7.4%), none judged drug-related (Mahlapuu et al., 2021).
  • Diabetic foot trial. One of 13 patients on LL-37 cream developed mild irritant contact dermatitis, which the authors attributed to wound fluid (Miranda et al., 2023).
  • Melanoma injections. A 63-year-old woman given 8 weekly injections developed multiple warty skin lesions about 45 days after starting. Biopsies showed atypical squamous growths, some resembling keratoacanthoma, a fast-growing skin tumor. All lesions resolved within 2 months of stopping (Dolkar et al., J Cutan Pathol 2018). The trial registry lists one case of squamous cell carcinoma among the 3 reported participants (NCT02225366).

Inflammation and autoimmunity

LL-37 is not a purely calming molecule. It helps drive the immune reaction to self-DNA in psoriasis (Lande et al., Nature 2007), and excess cathelicidin fragments are tied to rosacea (Yamasaki et al., Nat Med 2007). The effect of raising LL-37 levels in people with these conditions has not been studied.

Tumor growth

In mice, blocking LL-37 reduced the growth of human ovarian tumor grafts, and LL-37 drew stromal cells into tumors that fed new blood vessels (Coffelt et al., PNAS 2009). FDA likewise cites nonclinical evidence that LL-37 can promote tumors in some tissues (FDA, 2026). These are animal and cell findings, but they are a reason for caution in anyone with a current or past cancer.

Unknowns for injected, unregulated product

  • No human data exist on repeated injection of LL-37 under the skin or into muscle.
  • FDA lists immunogenicity and peptide-related impurities as concerns.
  • FDA also cites nonclinical evidence of harm to male reproduction; LL-37’s gene is naturally highly active in the testis (Agerberth et al., PNAS 1995).
  • The product used in the phase IIb trial was made by a defined synthesis, sterile-filtered and released against content and impurity specifications (Mahlapuu et al., 2021). By contrast, FDA flags peptide-related impurities and ingredient characterization as concerns for compounded LL-37.

Key takeaways

  • A natural human antimicrobial peptide. LL-37 is cut from hCAP18 and takes part in infection defense, wound closure, blood-vessel growth and inflammation.
  • Not an approved drug. It has been studied only as an investigational topical treatment for chronic ulcers and, in four patients, as an injection into melanoma.
  • Mixed wound results. A 34-patient trial was positive at the lowest concentration, but the 148-patient phase IIb trial found no overall benefit; a large-ulcer subgroup signal was post hoc.
  • No human data for recovery or injury use. No trial has tested it for muscle, tendon or training recovery, and no human half-life has been published.
  • Real safety questions. Links to psoriasis and rosacea, tumor-promoting effects in animal models, skin lesions in a melanoma patient, and FDA concerns about immunogenicity and male reproduction all argue for caution.

Sources

  1. Agerberth B, Gunne H, Odeberg J, et al. FALL-39, a putative human peptide antibiotic, is cysteine-free and expressed in bone marrow and testis. Proc Natl Acad Sci U S A. 1995;92(1):195–199. PubMed.
  2. Gudmundsson GH, Agerberth B, Odeberg J, et al. The human gene FALL39 and processing of the cathelin precursor to the antibacterial peptide LL-37 in granulocytes. Eur J Biochem. 1996;238(2):325–332. PubMed.
  3. Sørensen OE, Follin P, Johnsen AH, et al. Human cathelicidin, hCAP-18, is processed to the antimicrobial peptide LL-37 by extracellular cleavage with proteinase 3. Blood. 2001;97(12):3951–3959. PubMed.
  4. National Center for Biotechnology Information. PubChem Compound Summary for CID 16198951, LL-37. PubChem.
  5. Wang TT, Nestel FP, Bourdeau V, et al. Cutting edge: 1,25-dihydroxyvitamin D3 is a direct inducer of antimicrobial peptide gene expression. J Immunol. 2004;173(5):2909–2912. PubMed.
  6. Gombart AF, Borregaard N, Koeffler HP. Human cathelicidin antimicrobial peptide (CAMP) gene is a direct target of the vitamin D receptor and is strongly up-regulated in myeloid cells by 1,25-dihydroxyvitamin D3. FASEB J. 2005;19(9):1067–1077. PubMed.
  7. Heilborn JD, Nilsson MF, Kratz G, et al. The cathelicidin anti-microbial peptide LL-37 is involved in re-epithelialization of human skin wounds and is lacking in chronic ulcer epithelium. J Invest Dermatol. 2003;120(3):379–389. PubMed.
  8. Koczulla R, von Degenfeld G, Kupatt C, et al. An angiogenic role for the human peptide antibiotic LL-37/hCAP-18. J Clin Invest. 2003;111(11):1665–1672. PubMed.
  9. Lande R, Gregorio J, Facchinetti V, et al. Plasmacytoid dendritic cells sense self-DNA coupled with antimicrobial peptide. Nature. 2007;449(7162):564–569. PubMed.
  10. Yamasaki K, Di Nardo A, Bardan A, et al. Increased serine protease activity and cathelicidin promotes skin inflammation in rosacea. Nat Med. 2007;13(8):975–980. PubMed.
  11. Pütsep K, Carlsson G, Boman HG, Andersson M. Deficiency of antibacterial peptides in patients with morbus Kostmann: an observation study. Lancet. 2002;360(9340):1144–1149. PubMed.
  12. Wang Y, Agerberth B, Löthgren A, et al. Apolipoprotein A-I binds and inhibits the human antibacterial/cytotoxic peptide LL-37. J Biol Chem. 1998;273(50):33115–33118. PubMed.
  13. Grönberg A, Mahlapuu M, Ståhle M, et al. 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. PubMed.
  14. Mahlapuu M, Sidorowicz A, Mikosinski J, 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. PubMed; PMC.
  15. Miranda E, Bramono K, Yunir E, 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. PubMed; PMC.
  16. M.D. Anderson Cancer Center. Intratumoral injections of LL37 for melanoma (NCT02225366). ClinicalTrials.gov; results posted December 9, 2021. ClinicalTrials.gov.
  17. Dolkar T, Trinidad CM, Nelson KC, et al. Dermatologic toxicity from novel therapy using antimicrobial peptide LL-37 in melanoma: a detailed examination of the clinicopathologic features. J Cutan Pathol. 2018;45(7):539–544. PubMed.
  18. Zhao Y, Zhang H, Zhao Z, et al. Efficacy and safety of Oral LL-37 against the Omicron BA.5.1.3 variant of SARS-COV-2: a randomized trial. J Med Virol. 2023;95(8):e29035. PubMed.
  19. Coffelt SB, Marini FC, Watson K, et al. The pro-inflammatory peptide LL-37 promotes ovarian tumor progression through recruitment of multipotent mesenchymal stromal cells. Proc Natl Acad Sci U S A. 2009;106(10):3806–3811. PubMed.
  20. Food and Drug Administration. Certain bulk drug substances for use in compounding that may present significant safety risks (content current as of April 22, 2026). FDA.
  21. World Anti-Doping Agency. World Anti-Doping Code International Standard: Prohibited List 2026. WADA 2026 Prohibited List.