Educational reference, not medical advice. This page summarizes information from published research and regulatory filings for educational purposes. It is not a recommendation to use any compound and should not replace guidance from a licensed healthcare provider. Most peptides discussed here are not approved for the uses described.
What it is
LL-37 is the active form of the only human cathelicidin antimicrobial peptide, named for its 37-amino-acid length beginning with two leucines. The precursor protein hCAP-18 is stored in the secondary granules of neutrophils and in keratinocytes, mast cells, and epithelial cells throughout the body; proteolytic cleavage by proteinase 3 releases the active LL-37 fragment.
History
LL-37 was identified and named in 1995 by groups led by Gudmundsson and Agerberth at the Karolinska Institute. Research interest expanded rapidly through the late 1990s and 2000s as the peptide was shown to combine broad-spectrum antimicrobial activity with immunomodulatory effects on host cells — a dual role consistent with its presence in skin, gut, and lung mucosal surfaces. Its role in rosacea was characterized in a 2007 Nature Medicine paper showing elevated cathelicidin and serine protease activity in rosacea skin.
Regulatory status
There is no approved drug product based on LL-37 or its analogs. The most advanced clinical development to date has been Promore Pharma's PXL01 (an LL-37-derived peptide) for surgical adhesion prevention, which completed Phase II. The native LL-37 sequence itself is sold through research peptide suppliers and is not on any approved compounding list.
Mechanism
LL-37 is amphipathic — it adopts an α-helical structure on membrane surfaces, with hydrophobic residues on one face and cationic residues on the other. The published mechanisms include:
- Direct membrane disruption of gram-positive and gram-negative bacteria, fungi, and enveloped viruses at concentrations of 1–30 µM.
- Chemotaxis of neutrophils, monocytes, T cells, and mast cells via the formyl peptide receptor-like 1 (FPRL1).
- Promotion of keratinocyte and endothelial cell migration, contributing to wound re-epithelialization and angiogenesis.
- Modulation of inflammation through both pro- and anti-inflammatory pathways depending on context — neutralizing LPS at low doses, but capable of amplifying inflammation when overproduced (as in rosacea).
- Anti-biofilm effects at sub-MIC concentrations through inhibition of bacterial attachment.
Half-life and dosing intervals
Published estimates put the circulating half-life of LL-37 at approximately 4 to 6 hours after subcutaneous administration in rodent studies. Tissue distribution is broad; local concentrations at mucosal surfaces in vivo can transiently exceed plasma levels by an order of magnitude during infection.
There are no established human systemic doses. Topical formulations in early-phase human trials have used concentrations in the 0.1% to 1% range applied directly to wounds or surgical sites. Subcutaneous protocols described observationally in research channels typically use 100–500 µg per day.
Reconstitution example
LL-37 vials are typically 5 mg of lyophilized powder. A 5 mg vial reconstituted with 2 mL of bacteriostatic water yields 2.5 mg/mL. On a 1 mL U-100 insulin syringe, 4 units (0.04 mL) delivers 100 mcg. LL-37 is sensitive to repeated freeze-thaw cycles; small-volume reconstitution that can be used within the stability window is preferable.
What to know
- Limited human data for systemic use. Most clinical work has been topical. Systemic safety has not been characterized in controlled trials.
- Pro-inflammatory potential. Elevated cathelicidin is implicated in the pathophysiology of rosacea and certain autoimmune conditions, suggesting caution at high systemic doses.
- Storage. Refrigerate lyophilized vials. Reconstituted LL-37 should be stored at 2–8 °C and protected from freeze-thaw cycles.
- Reported side effects in user reports include injection-site reactions and transient flu-like symptoms; the safety profile of repeated systemic administration is not well characterized.
Sources
- 1.Vandamme D et al. (2012). A comprehensive summary of LL-37, the factotum human cathelicidin peptide. Cellular Immunology.
- 2.Gudmundsson GH et al. (1996). The human gene FALL39 and processing of the cathelin precursor to the antibacterial peptide LL-37 in granulocytes. European Journal of Biochemistry.
- 3.Carretero M et al. (2008). In vitro and in vivo wound healing-promoting activities of human cathelicidin LL-37. Journal of Investigative Dermatology.
- 4.Yamasaki K et al. (2007). Increased serine protease activity and cathelicidin promotes skin inflammation in rosacea. Nature Medicine.