LL-37

Humans possess exactly one cathelicidin, and that is LL-37. The name gives away the structure: two leucines at the N-terminal end and 37 amino acids in total. The peptide is released by proteolytic cleavage from the precursor protein hCAP-18, which is made in epithelia and leukocytes. Structurally it is amphipathic and helical, with a positive charge.

That charge is the key to its first function: LL-37 attaches to the negatively charged membranes of microorganisms and makes them leaky. In preclinical studies the spectrum covers bacteria, viruses and fungi. Against Pseudomonas aeruginosa it blocked biofilm formation in vitro at as little as 0.5 micrograms per millilitre, a fraction of the 64 micrograms per millilitre needed to inhibit growth.

The second function lies in immune regulation and repair:

• chemotaxis of leukocytes and modulation of cytokine production,
• involvement in wound healing,
• new vessel growth: LL-37 activated endothelial cells through the receptor FPRL1 and triggered angiogenesis in a rabbit hind-limb ischaemia model; mice lacking the corresponding cathelicidin were short of wound vessels.

Context also calls for a caveat: a 2021 phase 2b trial with 148 participants with chronic venous leg ulcers found no significant advantage for topical LL-37 over placebo in the overall group; only an after-the-fact analysis of large wounds hinted at an effect. Shifts in LL-37 levels seen in some chronic inflammatory conditions also make the peptide interesting for pathophysiological research.

We list LL-37 strictly as a research compound; this text is context, not a guide to use.

LL-37 is endogenous and largely well tolerated in studies. What you should still know:

• Injection site: mild redness or irritation is the most common local observation.
• Membrane action: the same property that makes microbial membranes leaky plausibly explains local irritation.
• Immune modulation: interventions in chemotaxis and cytokine production touch innate immunity; some chronic inflammatory conditions come with documented shifts in LL-37 levels.
• Evidence base: the characterisation comes mostly from preclinical models, one controlled human trial of topical LL-37 showed no significant advantage, and robust long-term data are missing.

This summary is no substitute for medical advice.

• An angiogenic role for the human peptide antibiotic LL-37/hCAP-18 - 2003 paper on new vessel growth via FPRL1, with rabbit and mouse models.
• Human host defense peptide LL-37 prevents bacterial biofilm formation - 2008 in vitro study on biofilm inhibition in Pseudomonas aeruginosa.
• Evaluation of LL-37 in healing of hard-to-heal venous leg ulcers: A multicentric prospective randomized placebo-controlled clinical trial - 2021 phase 2b trial with no significant advantage in the overall group.