LL-37
LL-37 is the only cathelicidin produced by humans. It is cleaved by proteinase 3 from the C-terminal end of the precursor protein hCAP-18, the product of the CAMP gene, and takes its name from the two leucines that open its 37 amino acid sequence. It is expressed by neutrophils, monocytes, and epithelial cells at barrier surfaces including skin, gut, and airway, where it functions as a front-line component of innate immunity rather than as a hormone or growth factor.
- class
- cathelicidin host defense peptide (CAMP gene product)
- sequence
- 37 amino acids, cationic amphipathic alpha helix
- half-life
- short in plasma (minutes to a few hours), protease sensitive
- route
- topical in clinical trials; subcutaneous in research use
- typical dose
- 50–200 mcg/day subcutaneous; 0.5–1.6 mg/mL topical in trials
- storage
- lyophilized cool and dark; reconstituted 2–8°C, 28-day max
LL-37 Reconstitution & Dosage Protocol
weekly dose · reduces side effects| Phase | Window | Weekly dose | Draw (U-100, 5mL BAC) | Note |
|---|---|---|---|---|
| Conservative start | Days 1–7 | 0.05 mg | 5 units· 0.05 mL | 50 mcg once daily subcutaneous. LL-37 is cytotoxic and hemolytic at high local concentrations, so the low end is the correct entry point rather than a token starting dose |
| Standard research range | Days 8–30 | 0.10 mg | 10 units· 0.10 mL | 100 mcg once daily. At 1 mg/mL (5 mg vial in 5 mL BAC water) this is 0.1 mL, which is 10 units on a U-100 syringe. Rotate injection sites, local irritation is the most common complaint |
| Upper anecdotal range | As tolerated | 0.20 mg | 20 units· 0.20 mL | 200 mcg daily is the top of commonly reported self-directed use. No human trial has established a safe systemic dose, so anything above this range has no supporting data at all |
| Topical wound protocol | Weeks 1–4 | 0.50 mg | 50 units· 0.50 mL | Clinical trials used a 0.5 mg/mL solution applied to the wound bed twice weekly for 4 weeks. This is a concentration, not a systemic dose. The 3.2 mg/mL arm performed no better than placebo |
| Off period | After 4 weeks | 0.00 mg | 0 units· 0.00 mL | Stop and reassess. LL-37 is an immune signaling peptide with documented autoimmune associations, so continuous open-ended use is not supported by the literature |
What is LL-37?
LL-37 is the only cathelicidin produced by humans. It is cleaved by proteinase 3 from the C-terminal end of the precursor protein hCAP-18, the product of the CAMP gene, and takes its name from the two leucines that open its 37 amino acid sequence. It is expressed by neutrophils, monocytes, and epithelial cells at barrier surfaces including skin, gut, and airway, where it functions as a front-line component of innate immunity rather than as a hormone or growth factor.
The peptide is cationic and amphipathic, folding into an alpha helix that inserts into and disrupts negatively charged bacterial membranes. That direct microbicidal action covers Gram-positive and Gram-negative bacteria, some fungi, and enveloped viruses, and it also neutralizes lipopolysaccharide, blunting the endotoxin-driven inflammatory cascade. Dürr and colleagues catalogued this dual antimicrobial and immunomodulatory profile in their 2006 review, which remains the standard reference on the molecule.
The repair-side interest comes from LL-37 signaling through the formyl peptide receptor FPR2 (FPRL1) on endothelial and epithelial cells. Koczulla and colleagues showed in 2003 that LL-37 drives angiogenesis and neovascularization through this receptor, and later work demonstrated that it stimulates airway epithelial proliferation and wound closure and accelerates re-epithelialization in human skin models. This is the mechanism the wound-healing trials were built on: recruit cells, promote new vessel growth, and close the wound, alongside keeping bacterial load down.
Human trial results are real but modest and confined to topical use. The 2014 first-in-man study in 34 patients with hard-to-heal venous leg ulcers tested 0.5, 1.6, and 3.2 mg/mL applied twice weekly for 4 weeks. The two lower concentrations improved healing (a roughly sixfold higher healing rate constant at 0.5 mg/mL versus placebo, p = 0.003) while the highest concentration was no better than placebo, an inverted dose response consistent with LL-37 cytotoxicity at high concentrations. The larger 2021 phase IIb HEAL LL-37 trial in 148 patients found no significant benefit across the full cohort, with a post hoc signal only in the subgroup with wounds of at least 10 cm2. LL-37 was safe and well tolerated in both trials.
The cautions are specific and worth understanding before use. Vitamin D directly upregulates CAMP transcription through the vitamin D receptor (Gombart 2005), so correcting a vitamin D deficiency raises endogenous LL-37 without any exogenous peptide. On the other side, excess cathelicidin activity is causally implicated in rosacea (Yamasaki 2007), and LL-37 complexed with self-DNA activates plasmacytoid dendritic cells through TLR9, a mechanism central to psoriasis and studied in lupus (Lande 2007). LL-37 is not FDA-approved for any indication and is sold in the United States for research purposes only. Subcutaneous dosing in particular has no published human protocol behind it, the trial data is topical.