LL-37 is the only cathelicidin family antimicrobial peptide expressed in humans, a 37-amino-acid α-helical peptide cleaved from the C-terminus of the hCAP-18 precursor protein. It is a central component of the innate immune system, expressed by neutrophils, epithelial cells and a wide range of tissues. The "LL-37" designation derives from the two N-terminal leucine residues and the 37-residue mature length. Research applications span direct antimicrobial activity, immunomodulation, wound healing and the broader interface between innate immunity and tissue repair.
LL-37 has two distinct mechanistic profiles: a direct antimicrobial mode and an immunomodulatory mode. The antimicrobial activity arises from the peptide's amphipathic α-helical structure and net positive charge (+6), which together permit selective insertion into the negatively-charged bacterial cell membrane. Membrane disruption follows through a "carpet" or "toroidal pore" mechanism, killing Gram-positive and Gram-negative bacteria, fungi and some enveloped viruses.
The immunomodulatory mode is mediated through binding to formyl peptide receptor 2 (FPR2) and the P2X7 receptor on immune cells, and through neutralisation of bacterial lipopolysaccharide (LPS) and lipoteichoic acid (LTA). Downstream effects include chemoattraction of neutrophils, monocytes and T-cells; modulation of dendritic-cell maturation; and attenuation of the LPS-induced inflammatory cascade.
LL-37 expression is strongly induced by the active vitamin D metabolite 1,25-dihydroxyvitamin D — a regulatory relationship that underpins much of the published research connecting vitamin D status to innate immune competence in respiratory and infectious-disease research.
LL-37 displays activity against a wide spectrum of clinically-relevant pathogens including methicillin-resistant Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa and Mycobacterium tuberculosis in published in vitro research. Of particular interest is anti-biofilm activity — published research has documented LL-37's ability to disrupt established biofilms, a property of growing translational interest given the role of biofilms in chronic infection.
The peptide has been studied in the context of inhaled antimicrobial therapy for cystic fibrosis lung infections, where its antimicrobial and LPS-neutralising activities may have complementary value.
Beyond direct antimicrobial activity, LL-37 plays a documented role in wound healing — promoting keratinocyte migration, angiogenesis and the resolution phase of inflammation. Diabetic ulcer research has documented reduced LL-37 expression in non-healing wounds, with topical LL-37 dosing accelerating closure in preclinical models.
The vitamin D regulation of LL-37 expression has been the subject of extensive research, providing molecular grounding for the epidemiological associations between vitamin D status and respiratory infection risk. The active 1,25-dihydroxyvitamin D metabolite induces LL-37 expression in monocytes, macrophages and keratinocytes via the vitamin D receptor / RXR transcriptional complex.