LL-37: Human Cathelicidin Antimicrobial Peptide
Endogenous 37-residue cationic peptide with broad antimicrobial and immunomodulatory activity. Investigational for infection, wound healing and chronic ulcers.
👥🐀 Human + animal
- Full name
- LL-37 / cathelicidin (hCAP-18 C-terminus)
- Class
- Cationic antimicrobial peptide
- Half-life
- Short in serum; longer bound to membranes
- Route
- Topical in trials; systemic under investigation
- Developer
- Academic; Pergamum/Promore Pharma (topical OP-145)
- Regulatory status
- No approval for systemic use; topical cathelicidin analogues in trials
What it is
LL-37 is the only human cathelicidin, cleaved from the hCAP-18 precursor by proteinase-3 at sites of infection or injury. It is produced by neutrophils, epithelial cells, and keratinocytes and forms part of the innate immune defence.
How it works
The cationic amphipathic α-helix disrupts bacterial membranes directly — active against Gram-positive, Gram-negative, and some enveloped viruses. Concentrations required for direct kill are high.
At lower concentrations LL-37 acts as an immunomodulator: chemotaxis of neutrophils, monocytes and T cells via formyl-peptide receptor 2; dampening of LPS-induced inflammation; promotion of keratinocyte migration and angiogenesis (relevant to wound healing).
What the research shows
Most translational evidence comes from topical applications for chronic wounds and ocular infection.
Gronberg A. et al. (2014) — hard-to-heal venous leg ulcers Phase 2
Grönberg A. et al., Wound Repair Regen 2014;22:613–621. 👥 Human studies
34 patients with chronic venous leg ulcers received topical LL-37 (0.5 or 1.6 mg/mL) or placebo.
Healing rate doubled in the 0.5 mg/mL group at 8 weeks; higher doses paradoxically showed no benefit.
Limitations: Small Phase 2; dose-response non-monotonic.
Lee H. et al. (2017) — antimicrobial activity characterisation
Lee H. et al., J Antibiot 2017;70:979–987 (representative). 🐀 Animal
In vitro and rodent skin-infection models show bactericidal activity against S. aureus and P. aeruginosa.
Modified LL-37 variants (shorter, more stable) are under development to reduce host-cell toxicity.
Limitations: Mainly pre-clinical; concentration-dependent toxicity.
Safety and limitations
Topical use was well tolerated at therapeutic concentrations; systemic LL-37 has not been clinically developed, partly because high concentrations can be cytotoxic and pro-inflammatory.
Over-expression has been implicated in rosacea and psoriasis — endogenous LL-37 is a double-edged sword.