LL-37

What Is LL-37?

LL-37 is the active 37-amino-acid fragment of human cathelicidin (hCAP-18, encoded by the CAMP gene), the body's own broad-spectrum antimicrobial peptide. It is part of the innate immune system's first line of defence and is produced by neutrophils, macrophages, and epithelial cells of the skin, lung, and gut.

The mechanism is multi-pronged. First, direct microbial killing: LL-37 inserts an amphipathic alpha-helix into bacterial, fungal, and enveloped-viral membranes, causing disruption and lysis. Second, biofilm dispersal at sub-inhibitory concentrations, the most-cited reason for its study in chronic infection models, since biofilms are what allow Borrelia, Staphylococcus, Pseudomonas, and Candida to persist through antibiotic exposure. Third, immunomodulation: LL-37 chemoattracts neutrophils, monocytes, and T cells, modulates Toll-like receptor signalling, and tunes cytokine output in either direction depending on context. Fourth, wound healing and angiogenesis through formyl peptide receptor-like 1 (FPR2) activation. Endogenous LL-37 expression is vitamin-D-dependent, since 1,25(OH)2D binding to the vitamin D receptor drives CAMP gene transcription, which is the mechanistic link behind the long-observed association between low vitamin D and infection susceptibility. LL-37 is also being studied for its role in the inflammatory pathology of rosacea and psoriasis, where its overexpression is pathogenic.