Also known as: CAP-18(106-137) · Cathelicidin LL-37 · FALL-39
LL-37 is the only human cathelicidin antimicrobial peptide (AMP), derived from the C-terminal cleavage of the CAP18 protein. It forms amphipathic α-helices that disrupt bacterial membranes and exhibits broad-spectrum activity against bacteria, fungi, and enveloped viruses, while simultaneously modulating innate immune responses and promoting wound healing.
LL-37 is produced primarily by neutrophils, NK cells, mast cells, and epithelial cells of the skin, gut, and respiratory tract. It is a front-line component of the innate immune defense, released rapidly at sites of infection or injury before adaptive immune responses are mobilized. Its name derives from its 37-amino-acid length and N-terminal Leucine-Leucine (LL) sequence.
Beyond direct antimicrobial activity, LL-37 has important immunomodulatory roles: it neutralizes bacterial LPS (preventing septic shock), triggers dendritic cell maturation, and acts as a chemoattractant for immune cells. It also promotes angiogenesis and re-epithelialization in wound healing — making it a multi-functional innate defense effector rather than a simple antibiotic.
LL-37 adopts an amphipathic α-helical structure in hydrophobic environments (bacterial membranes), allowing its positively charged face to electrostatically bind anionic bacterial phospholipids. It then inserts into and disrupts the membrane via a "carpet model" — disintegrating the lipid bilayer at high concentrations rather than forming discrete pores.
Unlike most conventional antibiotics, LL-37 can penetrate and disrupt established biofilms of Pseudomonas aeruginosa, S. aureus, and E. coli at sub-inhibitory concentrations by interfering with quorum sensing (via autoinducer binding) and destabilizing biofilm matrix polysaccharides.
LL-37 binds lipopolysaccharide (LPS/endotoxin) from gram-negative bacteria with high affinity, preventing LPS from engaging TLR4 on macrophages and avoiding the catastrophic cytokine storm of septic shock. This makes LL-37 a candidate for sepsis intervention.
LL-37 is an endogenous human peptide with a well-established safety profile at physiological concentrations. The main concern is cytotoxicity at high concentrations — maintain therapeutic window (1–10 µg/mL topically). LL-37 degrades rapidly in serum (half-life ~3–4 hours), limiting systemic exposure with parenteral routes. Vitamin D3 (5,000 IU/day) is a non-peptide strategy to upregulate endogenous LL-37 expression via the CAMP gene VDR response element.
Topical LL-37 for wound healing can be used continuously until wound closure. Injectable research protocols typically follow short cycles given the lack of long-term human safety data. Unlike many research peptides, LL-37 does not downregulate its own receptor with chronic use — it acts on diverse receptors (FPRL1, EGFR, TLR4) without known receptor desensitization.
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