LL-37

What it is

LL-37 is a 37-amino-acid peptide cleaved from hCAP18, the human cathelicidin antimicrobial protein, and is part of the innate immune system in skin, airways, and white blood cells. It appears in research on chronic wound healing, antimicrobial defence, angiogenesis, and tumour immunology. A synthetic version has been tested in Phase 1 and Phase 2 trials as a topical agent for leg and foot ulcers, but it is not an approved medicine in any market.

How it works

Beyond direct antimicrobial activity, preclinical work shows LL-37 activates endothelial cells through formyl peptide receptor-like 1 to drive new vessel growth, and supports keratinocyte re-epithelialisation of skin wounds. It can also activate plasmacytoid dendritic cells, the rationale for its study as an intratumoral immune stimulant.

Regulatory status

1. Cosmetic ingredient
2. Research compound
3. In clinical trials
4. Approved medicine

Not approved as a medicine by the FDA or the EMA. Some are registered in individual countries. Supplied for laboratory research only.

What published research is studying

• Healing of hard-to-heal venous leg ulcers (first-in-human and Phase 2b trials)
• Granulation and bacterial colonisation in mildly infected diabetic foot ulcers (Phase 2)
• Re-epithelialisation and angiogenesis in human skin explants and animal wound models
• Intratumoral injection in melanoma with cutaneous metastases (Phase 1/2, completed)

Key findings

1. 01

   In a first-in-human randomised, double-blind, placebo-controlled trial in 34 people with hard-to-heal venous leg ulcers, 4 weeks of topical LL-37 at the two lower concentrations reduced mean ulcer area by 68% and 50%, with healing rate constants about sixfold (p = 0.003) and threefold (p = 0.088) higher than placebo, while the highest concentration showed no difference from placebo.

   Grönberg A et al., Wound Repair Regen 2014
2. 02

   In the 148-patient Phase 2b HEAL LL-37 trial in hard-to-heal venous leg ulcers, topical LL-37 added to compression therapy did not significantly improve healing versus placebo in the full study population; a post hoc analysis suggested benefit only in wounds of at least 10 cm².

   Mahlapuu M et al., Wound Repair Regen 2021
3. 03

   In a 4-week randomised, double-blind, placebo-controlled trial in people with mildly infected diabetic foot ulcers, LL-37 cream produced a greater increase in granulation index than placebo at days 7, 14, 21, and 28, but did not lower wound-fluid IL-1α, TNF-α, or aerobic bacterial colonisation.

   Miranda E et al., Arch Dermatol Res 2023
4. 04

   In human skin, hCAP18/LL-37 levels peaked 48 hours after wounding and were absent from chronic ulcer edge epithelium, and blocking LL-37 with antibodies inhibited re-epithelialisation of organ-cultured human skin wounds in a concentration-dependent manner.

   Heilborn JD et al., J Invest Dermatol 2003
5. 05

   In preclinical models, LL-37 induced neovascularisation in the chick chorioallantoic membrane assay and in a rabbit hind-limb ischaemia model, and mice lacking CRAMP, the mouse counterpart of LL-37, showed reduced vascularisation during wound repair.

   Koczulla R et al., J Clin Invest 2003

How strong is the evidence?

Common questions