LL-37

This mechanistic study showed that LL-37 activates migration of human HaCaT keratinocytes in vitro, driving actin cytoskeleton reorganization and increased tyrosine phosphorylation of proteins in focal adhesion complexes. Using adenoviral gene transfer of LL-37 to full-thickness excisional wounds in diabetic, healing-impaired ob/ob mice, the peptide significantly enhanced re-epithelialization and granulation tissue formation in vivo. The work established that LL-37's benefit in wound repair is a direct pro-regenerative effect on host skin cells, distinct from its antimicrobial killing.

Beyond fighting germs, LL-37 helps skin heal. In lab dishes it prompted skin cells to move and close gaps, and in wounds on diabetic mice that normally heal poorly, delivering extra LL-37 sped up the regrowth of skin and healthy new tissue. This showed LL-37 actively helps the body rebuild wounded skin, not just keep it clean.

This peer-reviewed review synthesizes LL-37's dual role as a broad-spectrum, membrane-disrupting antimicrobial peptide and a multifunctional immunomodulator. It details how the cationic, amphipathic 37-residue peptide (cleaved from hCAP18) permeabilizes microbial membranes, neutralizes LPS/endotoxin, and inhibits biofilms, while also driving chemotaxis of neutrophils, monocytes and lymphocytes, modulating cytokine production, and promoting angiogenesis and wound healing. Being a review, it is mechanistic and integrative rather than reporting new primary experimental data.

This overview pulls together what is known about LL-37, a natural peptide our own immune cells make. It explains the two big jobs the peptide does: punching holes in bacteria to kill them, and acting as a signal that recruits and coordinates immune cells while helping tissues heal. It is a useful map of why this one small molecule matters across infection, inflammation and repair.

This phase IIb double-blind, randomized, placebo-controlled clinical trial (HEAL LL-37) tested topical LL-37 (0.5 or 1.6 mg/mL) plus compression therapy in 148 patients with hard-to-heal venous leg ulcers. The primary efficacy analysis over the full population found no statistically significant improvement in healing versus placebo, though the 0.5 mg/mL dose showed a significant odds ratio (~3.25) for reaching 50% wound closure, and a post hoc analysis found significant benefit in patients with large wounds (>=10 cm2). Treatment was safe and well tolerated across doses.

This was a real human trial in patients with stubborn leg ulcers that will not heal. Applying LL-37 to the wound was safe, but overall it did not clearly beat placebo at healing the ulcers; hints of benefit appeared for partial wound closure and for the largest wounds. It shows the peptide is promising and safe but not yet a proven cure, which is why researchers are still refining the dose and target patients.