Cathelicidin antimicrobial peptide (LL-37) and Pro-inflammatory cytokines (LL-37/Cytokines)

LL-37 is the sole human member of the cathelicidin family of antimicrobial peptides, primarily derived from the proteolytic cleavage of the hCAP18 precursor (UniProt: P49913). While it serves a critical protective role against pathogens, LL-37 also functions as a potent pro-inflammatory mediator by forming complexes with self-nucleic acids to activate Toll-like receptors (TLRs), particularly TLR7 and TLR9 in plasmacytoid dendritic cells (PubMed: 17914396). This activation leads to the robust production of Type I Interferons and the subsequent release of various pro-inflammatory cytokines such as TNF-alpha, IL-6, and IL-17. The synergy between LL-37 and these cytokines is a hallmark of chronic inflammatory skin conditions like psoriasis and rosacea, where their overabundance creates a self-sustaining loop of immune activation (PubMed: 21939738). Therapeutic strategies often focus on neutralizing specific cytokines (e.g., using Adalimumab for TNF or Secukinumab for IL-17) or developing agents that inhibit LL-37's ability to trigger downstream inflammatory pathways. Understanding this complex interaction is essential for developing targeted treatments that can balance necessary antimicrobial defense with the prevention of pathological autoinflammation.

Other names

LL37CAMPhCAP18CathelicidinInflammatory cytokinesPro-inflammatory mediators

Therapeutic intervention typically involves the neutralization of specific downstream cytokines using monoclonal antibodies or the modulation of LL-37 activity to prevent the formation of inflammatory complexes with nucleic acids (PubMed: 24613454).