LL-37 — Antimicrobial Peptide — Peptides

Overview

LL-37 is the only cathelicidin antimicrobial peptide (AMP) found in humans, derived from the C-terminal cleavage of the 18 kDa human cathelicidin antimicrobial protein (hCAP18) by proteinase 3. It is a 37-amino-acid alpha-helical peptide with broad-spectrum antimicrobial activity against bacteria, fungi, viruses, and parasites. LL-37 is produced by neutrophils, macrophages, epithelial cells, and keratinocytes as a critical component of the innate immune system. Beyond direct antimicrobial killing (through membrane disruption of pathogens), LL-37 has immunomodulatory functions including chemokine induction, anti-endotoxin activity, modulation of dendritic cell differentiation, and wound healing promotion. LL-37 expression is induced by vitamin D — the vitamin D receptor directly upregulates cathelicidin gene transcription, providing the molecular basis for vitamin D's role in innate immunity. Deficiency of LL-37 is associated with increased susceptibility to infections, chronic wounds, and inflammatory diseases. Exogenous LL-37 has been investigated for treatment of chronic wounds, drug-resistant infections, and biofilm-associated infections. However, all human use remains investigational, and LL-37 is available only as a research peptide. Stability and delivery remain significant challenges due to the peptide's susceptibility to proteolytic degradation.

Indications

• Investigational: Chronic wound healing (topical)
• Investigational: Drug-resistant bacterial infections
• Investigational: Biofilm disruption
• Research only: Immune modulation and antimicrobial support

Mechanism of Action

LL-37's amphipathic alpha-helical structure inserts into microbial membranes, forming pores that cause pathogen lysis

Dosing

Evidence Grade

GRADE D

Safety & Contraindications

• NO human clinical safety data for therapeutic use
• Injection site reactions possible
• Theoretical risk of excessive inflammation at high concentrations
• Susceptible to proteolytic degradation — stability issues
• Research compound only — not for clinical use
• Quality and purity concerns with non-pharmaceutical sources