LL-37

Also known as: Cathelicidin, hCAP-18

**Mechanism of Action** LL-37, the C-terminal active fragment of the human cathelicidin hCAP-18, exerts broad-spectrum antimicrobial activity by disrupting bacterial membranes via electrostatic interactions with negatively charged lipid bilayers, leading to pore formation and cell lysis. Beyond direct killing, LL-37 modulates innate immunity by chemoattracting immune cells (e.g., neutrophils, monocytes, T cells) through formyl peptide receptor-like 1 (FPRL1) and by suppressing pro-inflammatory cytokine release (e.g., TNF-α, IL-6) while promoting anti-inflammatory mediators (e.g., IL-10). It also enhances wound healing by stimulating keratinocyte migration, angiogenesis, and re-epithelialization via transactivation of epidermal growth factor receptor (EGFR) and induction of vascular endothelial growth factor (VEGF). **Key Research Findings** Preclinical studies demonstrate LL-37’s efficacy against multidrug-resistant bacteria (e.g., MRSA, *Pseudomonas aeruginosa*) and biofilms, with synergistic effects when combined with conventional antibiotics. In murine wound models, topical LL-37 accelerates closure and reduces infection, while in respiratory models, it attenuates inflammation in cystic fibrosis and COPD. Elevated LL-37 levels are linked to psoriasis pathogenesis, whereas deficiency correlates with increased susceptibility to infections in atopic dermatitis and chronic wounds. Notably, LL-37 can form amyloid-like fibrils under certain conditions, potentially contributing to cytotoxicity at supraphysiological concentrations. **Clinical Relevance** Despite robust preclinical evidence, LL-37 remains in preclinical development due to challenges in stability, toxicity at high doses, and cost-effective synthesis. Clinical translation focuses on topical formulations for chronic wounds, diabetic ulcers, and catheter-associated infections, as well as inhaled therapies for respiratory infections. Its dual antimicrobial and immunomodulatory profile positions LL-37 as a promising candidate for combating antibiotic resistance, though further optimization of delivery and safety is required before human trials. For research purposes only — not medical advice.

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