Overview
Pharmacokinetically, LL-37 has a very short plasma half-life (~30–60 minutes) due to rapid degradation by serine proteases (e.g., kallikreins) and metalloproteinases. Subcutaneous delivery provides a local depot effect with slower systemic absorption. At the tissue level, it upregulates keratinocyte migration via PI3K/Akt and activates VEGF-A-mediated neovascularization. In immune cells, it promotes monocyte chemotaxis, mast cell degranulation, and dendritic cell maturation, while inhibiting apoptosis of neutrophils — extending their antimicrobial activity window.
Proposed mechanism
LL-37 exerts antimicrobial effects by inserting into and disrupting bacterial cell membranes, creating pores that lead to membrane depolarization and cell death, primarily through electrostatic interactions with negatively charged lipopolysaccharides on bacterial surfaces. It also acts as an immunomodulatory agent by binding to receptors including FPRL1 (formyl peptide receptor-like 1), TLR4, and purinergic receptors, activating downstream signaling cascades involving MAPK, NF-κB, and PI3K/Akt pathways that regulate cytokine production, cell migration, and angiogenesis. Additionally, LL-37 promotes wound healing by stimulating keratinocyte migration, angiogenesis via VEGF induction, and re-epithelialization of damaged tissue.
What the evidence supports
Human data exists but the trials are small, short-term, or not yet replicated.
Graded Human-limited
Human data that exists but is thin: open-label work, single-arm studies, small cohorts, or observational follow-up without randomisation.
Key citations
Representative primary sources, including results that did not favour the compound.
- [1]
LL-37: The only human member of the cathelicidin family of antimicrobial peptides
· Biochimica et Biophysica Acta (BBA) - Biomembranes, 1838(10):2503-2517 · 2014
- [2]
An antimicrobial peptide regulates tumor-associated macrophage trafficking via the chemokine receptor CCR2
· Immunity, 30(4):595-607 · 2009
- [3]
Topical treatment with LL-37 is beneficial for chronic venous leg ulcers: a randomized controlled trial
· Wound Repair and Regeneration · 2020
- [4]
The cathelicidin anti-microbial peptide LL-37 is involved in re-epithelialization of human skin wounds and is lacking in chronic ulcer epithelium
· Journal of Investigative Dermatology, 120(3):379-389 · 2003
Citation records in this build are illustrative placeholders for the design.
Reference information for research purposes. Not medical advice, and not a recommendation to use any compound. Many entries describe substances that are not approved for human use.