Summary

LL-37 is the active fragment of the only human cathelicidin antimicrobial peptide (hCAP-18), encoded by the CAMP gene. It plays a key role in innate immunity, exhibiting broad-spectrum antimicrobial activity against bacteria, fungi, and viruses, while also modulating the immune response. Research has explored its potential in wound healing, infection control, inflammatory conditions, and even cancer therapeutics.

Mechanism

LL-37 adopts an amphipathic α-helical conformation that enables it to bind to and disrupt negatively charged microbial membranes, causing cell lysis. It also functions as an immunomodulator: neutralising LPS (reducing endotoxic shock), acting as a chemoattractant for immune cells, and modulating inflammatory signalling pathways including TLR activation.

Evidence base

The evidence base for LL-37 is substantial in in vitro and preclinical models. It demonstrates broad-spectrum antimicrobial activity against bacteria (including MRSA), fungi, and enveloped viruses. Clinical translation has been limited — the LL-37-derived peptide pexiganan reached Phase III trials for diabetic foot ulcers but was not approved. LL-37 is also implicated in autoimmune pathology (psoriasis, lupus) where LL-37–nucleic acid complexes activate dendritic cells. Evidence grade: moderate (strong in vitro, limited clinical translation).

Protocols

In research contexts, LL-37 is typically used at 1–50 µg/mL in vitro. The LL-37-derived peptide pexiganan was studied as a 0.8–1% topical cream applied 1–2 times daily for up to 28 days in clinical trials. There are no established human dosing guidelines for LL-37 itself as an unlicensed research peptide. Researchers should consult primary literature for specific experimental protocols.

LL-37 is not a licensed medicine in the UK and is not controlled under the Misuse of Drugs Act. It is legal to purchase and possess as a research chemical. The MHRA has not issued specific guidance on LL-37. Any use in clinical trials would fall under the MHRA's investigational medicinal products framework.

Vendor notes

Vendor links will be added as verified suppliers are identified. See the Vendor Vetting Guide for guidance on evaluating peptide suppliers.

References

  1. Dürr UH, Sudheendra US, Ramamoorthy A. LL-37, the only human member of the cathelicidin family of antimicrobial peptides. Biochim Biophys Acta. 2006;1758(9):1408-1425. doi:10.1016/j.bbamem.2006.03.030
  2. Zanetti M. Cathelicidins, multifunctional peptides of the innate immunity. J Leukoc Biol. 2004;75(1):39-48. doi:10.1189/jlb.0403147
  3. Ganguly D, Chamilos G, Lande R, et al. Self-RNA-antimicrobial peptide complexes activate human dendritic cells through TLR7 and TLR8. J Exp Med. 2009;206(9):1983-1994. doi:10.1084/jem.20090480
  4. Guk J, Kim H, Choi J, et al. Development of antimicrobial peptide-based agents for biomedical applications. J Microbiol Biotechnol. 2019;29(8):1183-1192. doi:10.4014/jmb.1907.07029
  5. Gottler LM, Ramamoorthy A. Structure, membrane orientation, mechanism, and function of pexiganan — a highly potent antimicrobial peptide designed from magainin. Biochim Biophys Acta. 2009;1788(9):1680-1686. doi:10.1016/j.bbamem.2008.10.009
  6. Lande R, Gregorio J, Facchinetti V, et al. Plasmacytoid dendritic cells sense self-DNA coupled with antimicrobial peptide. Nature. 2007;449(7162):564-569. doi:10.1038/nature06116
  7. Lipsky BA, Holroyd KJ, Zasloff M. Topical antimicrobial therapy for treating chronic foot ulcers in diabetes: a review of pexiganan acetate. Expert Opin Investig Drugs. 2008;17(7):933-942. doi:10.1517/13543784.17.7.933
  8. Nuding S, Zabel LT, Enders C, et al. Antibacterial activity of human defensins against anaerobic intestinal bacterial species. Microbes Infect. 2014;16(7):532-541. doi:10.1016/j.micinf.2014.03.011