LL-37

Overview

LL-37 is the only human cathelicidin antimicrobial peptide — a 37-amino-acid peptide (starting with two leucines) cleaved from the hCAP-18 precursor. It has broad-spectrum antimicrobial activity and immunomodulatory roles, but is also implicated in the pathogenesis of autoimmune and inflammatory skin diseases including psoriasis, rosacea, and lupus. Not FDA-approved; research-use only.

Mechanism of Action

LL-37 disrupts bacterial, fungal, and some viral membranes through electrostatic interactions with anionic phospholipids. It is chemotactic for neutrophils, monocytes, and T cells via the formyl peptide receptor FPR2 (FPRL1), modulates TLR signaling, promotes angiogenesis and re-epithelialization, and can complex with self-DNA/RNA to activate plasmacytoid dendritic cells — a mechanism linked to autoimmune pathology.

Research Summary

A small Phase 1/2 randomized trial (Grönberg et al., 2014) showed topical LL-37 accelerated healing of hard-to-heal venous leg ulcers. In vitro work (Overhage et al., 2008) demonstrated biofilm prevention at sub-MIC concentrations against Pseudomonas aeruginosa. LL-37 has also been identified as a T-cell autoantigen in moderate-to-severe psoriasis (Lande et al., 2014) and is implicated in rosacea, lupus, and atherosclerosis. Grey-market injectable protocols for 'chronic Lyme,' 'biofilm infections,' and 'mold illness' are not supported by clinical trial evidence.

Dosing Information

Reported Side Effects

• Injection site pain and redness (limited human injection data)
• Theoretical cytokine release with systemic dosing
• Potential to trigger or worsen autoimmune/inflammatory skin disease (psoriasis, rosacea, lupus flares) given LL-37's documented role in their pathogenesis
• Flu-like symptoms

Research References

• LL-37, the only human member of the cathelicidin family of antimicrobial peptides (Dürr et al., 2006) (2006)
• Human host defense peptide LL-37 prevents bacterial biofilm formation (Overhage et al., 2008, Infect Immun) (2008)
• Treatment with LL-37 is safe and effective in enhancing healing of hard-to-heal venous leg ulcers: a randomized, placebo-controlled clinical trial (Grönberg et al., 2014) (2014)
• The antimicrobial peptide LL37 is a T-cell autoantigen in psoriasis (Lande et al., 2014, Nat Commun) (2014)