Hard-to-heal venous leg ulcers — randomised clinical trial
Phase IIStudies report improved wound healing with topical LL-37 compared with placebo.
— Grönberg et al. 2014, Wound Repair Regen 22(5):613-621 (PMID 25041740)
Human cathelicidin antimicrobial peptide (immunology research) Limited Human Data
LL-37
Also Known As: Cathelicidin LL-37, hCAP-18(134-170), CAMP
LL-37 is the only human cathelicidin: a 37-residue peptide proteolytically released from the precursor protein hCAP-18 (gene CAMP). It is produced by neutrophils, keratinocytes, mucosal epithelial cells and several other cell types. LL-37 is described as having both direct antimicrobial activity against bacteria, fungi and enveloped viruses, and broad immunomodulatory functions (chemotaxis, modulation of TLR signalling, wound-healing promotion). It has been clinically investigated, notably in a randomised study of hard-to-heal venous leg ulcers (Grönberg 2014). Limited human data. Research use only.
Identity & Chemistry
- Amino Acid Sequence
- LLGDFFRKSKEKIGKEFKRIVQRIKDFLRNLVPRTES (37-residue C-terminal fragment of the human cathelicidin precursor hCAP-18, the only human cathelicidin)
- Molecular Formula
- C₂₀₅H₃₄₀N₆₀O₅₃
- Molecular Weight
- 4493.33 g·mol⁻¹
- CAS Number
- 154947-66-7
- PubChem CID
- 16133745
- IUPAC Name
- See PubChem CID 16133745 for the structural representation of the 37-residue peptide.
Mechanism of Action
Studies report direct membranolytic antimicrobial activity together with immunomodulatory effects via FPR2 / P2X7-receptor engagement, chemotaxis and TLR modulation. Observed in research settings.
LL-37 has a dual identity: direct antimicrobial peptide (AMP) through membrane disruption, and endogenous modulator of innate immunity through receptor-mediated signalling. This dual role explains why LL-37 dysregulation is implicated in several skin conditions (rosacea, psoriasis) and in wound-healing biology.
Molecular Targets
- Microbial lipid membranes (direct membranolytic activity)
- FPR2 (formyl peptide receptor 2) — host-side immunomodulatory effects
- P2X7 purinergic receptor (reported)
Signaling Pathways
- Membrane permeabilization of pathogenic microorganisms
- Chemotaxis of neutrophils, monocytes and T cells
- Modulation of TLR / NF-κB signalling
Research Applications
The in-vitro and animal evidence base for LL-37 is extensive; human clinical data are limited to a few small studies, most notably the randomised venous-leg-ulcer trial (Grönberg 2014).
Antimicrobial activity — in vitro
in vitroStudies report broad antimicrobial activity against gram-negative and gram-positive bacteria, Candida species and enveloped viruses.
— Dürr et al. 2006, BBA 1758(9):1408-1425 (PMID 16716248, review)
Clinical Status
Regulatory Status
LL-37 is NOT approved as a pharmaceutical compound — by the FDA or EMA. It is an endogenous human peptide; synthetic preparations are research compounds only.
Highest Trial Phase
Small Phase 2 wound-healing trial (Grönberg 2014)
Safety Profile
Observed in research settings
Limited human data. The topical use in the Grönberg 2014 trial was described as safe; systemic pharmacovigilance data do not exist. Observed in research settings.
Adverse Events Reported in Studies
- Topical application: local irritation (reported, infrequent)
References
-
Dürr UH, Sudheendra US, Ramamoorthy A LL-37, the only human member of the cathelicidin family of antimicrobial peptides Biochimica et Biophysica Acta 2006;1758(9):1408-1425. 2006 .
-
Vandamme D, Landuyt B, Luyten W, Schoofs L A comprehensive summary of LL-37, the factotum human cathelicidin peptide Cellular Immunology 2012;280(1):22-35. 2012 .
-
Grönberg A, Mahlapuu M, Ståhle M, Whately-Smith C, Rollman O Treatment with LL-37 is safe and effective in enhancing healing of hard-to-heal venous leg ulcers: a randomized, placebo-controlled clinical trial Wound Repair and Regeneration 2014;22(5):613-621. 2014 .
Frequently Asked Questions
What is LL-37?
LL-37 is the only human cathelicidin: a 37-residue peptide produced by the body as part of innate immune defence. Synthetic LL-37 preparations are used for research.
Is LL-37 an approved medicine?
No. LL-37 is not approved as a pharmaceutical product by the FDA, EMA or any other regulator.
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