LL-37: evidence, FDA status and research

Sold for

LL-37 is sold as an injectable 'natural antibiotic' that fights infections, breaks up biofilms, heals wounds, and modulates immunity.

Studies say

Topical LL-37 has two small wound-healing trials with mixed results, the body's own LL-37 is well studied and drives inflammation in psoriasis and rosacea, and there are no human data on injecting it, so the evidence for the marketed use is grade C.

Why grade C. Two randomized placebo-controlled trials exist, both of LL-37 applied topically to chronic wounds: 148 patients with venous leg ulcers (negative on the primary endpoint) and a smaller diabetic foot ulcer trial. The injected 'immune support' use sold online has no human data at all. The rest of the human literature is observational work on the body's own LL-37 in wounds, psoriasis, and rosacea, plus cell and mouse mechanism studies. For the use it is sold for, that is C. ¹⁵¹⁶

FDA. Not approved by the FDA for any use and sold as a research chemical. LL-37 was nominated for the FDA's compounding bulk-substances list and placed in Category 2 (significant safety risk); the nomination was withdrawn, the FDA removed it from the category in April 2026, and a Pharmacy Compounding Advisory Committee review is planned before the end of February 2027. ²³⁴

Written from 16 cited sources. Last refreshed 2026-10-27. Not physician reviewed.

Evidence checklist

Randomised controlled trial Two topical wound RCTsyes
Human study over 100 people Venous ulcer trial, 148 patientsyes
More than one research group Article does not say who ran the trialsno information
Clinical outcomes, not surrogate markers Ulcer healing mixed; one negativeno
Human safety data beyond case reports Topical only; no injected human datano

Drawn from the cited studies below. A dash means the sources give no information.

What it is

LL-37 is the only cathelicidin antimicrobial peptide humans make. It is a 37-amino-acid fragment starting with two leucines, cut from the tail of a precursor protein called hCAP18 by the enzyme proteinase 3 after neutrophils release it. Neutrophils, skin cells, and the lining of the gut, lungs, and urinary tract all produce it, and levels rise sharply during infection and injury. ⁵⁶¹⁴

As a product, LL-37 is a synthetic copy of that sequence sold online as a lyophilized powder for injection. No company has taken injectable LL-37 into clinical trials. The trials that exist used it as a topical gel or cream on chronic wounds. ¹⁵¹⁶

How it works

The peptide is positively charged and forms a helix in contact with membranes, which lets it punch through bacterial membranes and kill Gram-positive and Gram-negative bacteria, fungi, and some enveloped viruses directly. It also binds lipopolysaccharide, the endotoxin from Gram-negative bacteria, and blunts its inflammatory effect. ¹⁴

LL-37 is also a signaling molecule. It attracts neutrophils, monocytes, and T cells through the formyl peptide receptor FPRL1, drives skin cells to migrate and close wounds, and stimulates new blood vessel growth in endothelial cells through prostaglandin E2. The CAMP gene that encodes it has a vitamin D response element, so active vitamin D switches it on; this is the mechanistic link between vitamin D status and resistance to infections such as tuberculosis. ⁵⁷⁸⁹¹⁰

What human research shows

The HEAL LL-37 trial randomized 148 patients with hard-to-heal venous leg ulcers to one of two strengths of topical LL-37 or placebo alongside compression. In the full population there was no significant difference in healing. A post hoc subgroup with ulcers of at least 10 square centimeters did better on LL-37, which the authors flagged for a follow-up trial. A smaller double-blind trial in Jakarta applied LL-37 cream or placebo to mildly infected diabetic foot ulcers over four weeks and found consistently greater granulation tissue in the LL-37 group, without the expected drop in inflammatory cytokines or bacterial counts. ¹⁵¹⁶

Observational work in patients shows why the peptide is double-edged. Chronic ulcers lack LL-37 at the wound edge, which supports the wound-healing rationale. But in psoriasis LL-37 binds the patient's own DNA and RNA and converts them into triggers for plasmacytoid dendritic cells, and it is a target of autoreactive T cells; in rosacea, abnormal processing produces LL-37 fragments that drive the facial inflammation. ⁷¹¹¹²¹³

Study	Model	Finding
HEAL LL-37 venous ulcer trial (2021)	Humans, n=148 with hard-to-heal venous leg ulcers, randomized double-blind placebo-controlled phase 2b, topical	No significant improvement in healing in the full population; a post hoc benefit in ulcers of at least 10 square centimeters. ¹⁵
LL-37 cream in diabetic foot ulcers (2023)	Humans, randomized double-blind placebo-controlled, topical, 4 weeks	Greater granulation tissue on LL-37 at every time point; no change in cytokines or bacterial counts. ¹⁶
LL-37 in psoriasis (Lande 2007)	Human skin samples and cell culture	LL-37 binds self-DNA and triggers interferon production by plasmacytoid dendritic cells, breaking tolerance in psoriasis. ¹²
Cathelicidin in rosacea (Yamasaki 2007)	Human skin samples and mice	Rosacea skin has excess cathelicidin and abnormal LL-37 fragments that reproduce the inflammation when injected into mice. ¹³
Vitamin D regulation of the CAMP gene (Gombart 2005)	Human cell lines and bone marrow cells	Active vitamin D switches on the gene encoding LL-37 through a vitamin D response element found only in primates. ⁹

Safety

In the two topical trials, LL-37 was well tolerated at the concentrations used, with no serious drug-related events. There are no data on injected LL-37 in humans, so the systemic side-effect profile is unknown. ¹⁵¹⁶

The mechanistic literature raises specific concerns for the injected use. LL-37 drives interferon production and T cell autoimmunity in psoriasis, promotes inflammation in rosacea, and stimulates blood vessel growth in a way that has been linked to tumor biology in ovarian, breast, and lung cancers. Whether exogenous LL-37 worsens any of these in people has not been tested; that is the point. The FDA's earlier Category 2 placement cited the lack of safety data. ²⁸¹¹¹²¹³

Questions for your clinician

Is there any human data on injected LL-37?
Could it worsen psoriasis, rosacea or other inflammatory conditions?
What does the negative venous ulcer trial mean for wound use?

Questions people ask

Is there an approved form of LL-37?

No. It has no approved form. The FDA listed it as a significant safety risk for compounding; after the nomination was withdrawn in 2026 it was removed from that category pending an advisory committee review, which does not make it legal to compound or sell for human use. ²³⁴

Which jobs does LL-37 carry out in the body?

It kills bacteria directly, neutralizes endotoxin, recruits immune cells, helps skin wounds close, and stimulates blood vessel growth. Neutrophils and epithelial cells release it during infection and injury. ⁵⁷⁸¹⁴

What link is there between vitamin D and LL-37?

The gene for LL-37 has a vitamin D response element, so active vitamin D increases its production. In human macrophages, this pathway is how Toll-like receptor signaling leads to killing of tuberculosis bacteria, and low vitamin D blunts it. ⁹¹⁰

Could LL-37 aggravate an autoimmune disease?

The body's own LL-37 is a driver of psoriasis, where it turns self-DNA into an interferon trigger and is an autoantigen for T cells, and of rosacea. Whether injecting extra LL-37 worsens these conditions has not been tested in people. ¹¹¹²¹³

What has human clinical research examined?

Only topical use on chronic wounds: a 148-patient venous ulcer trial that missed its primary endpoint and a small diabetic foot ulcer trial that showed more granulation tissue. No injected LL-37 trial exists. ¹⁵¹⁶

Citations

Biochem Biophys Res Commun 2020: LL-37 antiviral and immunomodulatory activity doi.org
FDA: Certain bulk drug substances for use in compounding may present significant safety risks fda.gov
FDA: Bulk drug substances nominated for use in compounding under section 503A, category list fda.gov
FDA: Pharmacy Compounding Advisory Committee meetings fda.gov
De Yang 2000, J Exp Med: LL-37 uses FPRL1 to chemoattract neutrophils, monocytes and T cells pubmed.ncbi.nlm.nih.gov
Sorensen 2001, Blood: hCAP-18 is processed to LL-37 by proteinase 3 pubmed.ncbi.nlm.nih.gov
Heilborn 2003, J Invest Dermatol: LL-37 in re-epithelialization of skin wounds and lacking in chronic ulcers pubmed.ncbi.nlm.nih.gov
Salvado 2013, Arterioscler Thromb Vasc Biol: LL-37 induces angiogenesis via PGE2-EP3 signaling pubmed.ncbi.nlm.nih.gov
Gombart 2005, FASEB J: CAMP gene is a direct target of the vitamin D receptor pubmed.ncbi.nlm.nih.gov
Liu 2006, Science: Toll-like receptor triggering of a vitamin D-mediated antimicrobial response pubmed.ncbi.nlm.nih.gov
2025, Front Immunol: Post-translational modifications of the autoantigen LL37 in psoriasis pubmed.ncbi.nlm.nih.gov
Lande 2007, Nature: Plasmacytoid dendritic cells sense self-DNA coupled with antimicrobial peptide pubmed.ncbi.nlm.nih.gov
Yamasaki 2007, Nat Med: Serine protease activity and cathelicidin promote skin inflammation in rosacea pubmed.ncbi.nlm.nih.gov
De Smet 2005, Biotechnol Lett: Human antimicrobial peptides, defensins, cathelicidins and histatins pubmed.ncbi.nlm.nih.gov
Gronberg 2021, Wound Repair Regen: LL-37 in hard-to-heal venous leg ulcers, randomized placebo-controlled trial pubmed.ncbi.nlm.nih.gov
2023, Arch Dermatol Res: LL-37 cream in diabetic foot ulcer, randomized double-blind controlled trial pubmed.ncbi.nlm.nih.gov