LL-37

LL-37 is a 37-amino acid peptide that represents the active, mature form of human cathelicidin (hCAP18), the only cathelicidin antimicrobial peptide found in humans. It is produced by immune cells (particularly neutrophils and macrophages), epithelial cells, and keratinocytes, and serves as a crucial component of the innate immune system's first line of defense. The peptide gets its name from its two N-terminal leucine (L) residues and its total length of 37 amino acids.

LL-37 exhibits broad-spectrum antimicrobial activity against gram-positive and gram-negative bacteria, enveloped viruses, and fungi. It works by directly disrupting microbial membranes through electrostatic interactions with negatively charged lipid bilayers, essentially punching holes in pathogen cell membranes. However, its role extends far beyond simple antimicrobial activity — LL-37 is now recognized as a multifunctional host defense peptide with important roles in immune signaling, inflammation modulation, and tissue repair.

The immunomodulatory properties of LL-37 are extensive. It can recruit immune cells to sites of infection, modulate toll-like receptor signaling, influence dendritic cell differentiation, and regulate the balance between pro-inflammatory and anti-inflammatory responses. It has been shown to neutralize bacterial lipopolysaccharide (LPS), reducing potentially harmful inflammatory responses to bacterial components. These properties make LL-37 a key player in coordinating immune responses rather than simply killing pathogens.

Research interest in LL-37 has expanded significantly, with investigations into its potential therapeutic applications for chronic infections, biofilm disruption, wound healing, and even cancer. Studies have shown that LL-37 can disrupt bacterial biofilms — organized communities of bacteria that are resistant to conventional antibiotics — making it relevant to chronic infection management. The peptide has also demonstrated the ability to promote angiogenesis and wound healing, and some research has explored its effects on tumor cell viability. Synthetic LL-37 is available for research purposes and has attracted interest in the integrative medicine community for immune support applications.