LL-37 is the only human cathelicidin-derived antimicrobial peptide, cleaved from the precursor hCAP-18 and studied for both direct microbicidal activity and immunomodulation.
Key Takeaways
- The 37-residue peptide is released by proteolytic cleavage of hCAP-18, chiefly by proteinase 3 in neutrophils.
- The peptide can be pro- or anti-inflammatory depending on context and concentration, and it interacts with receptors including FPR2 and P2X7.
- LL-37 complexes with self-DNA and self-RNA have been studied in psoriasis and lupus as drivers of interferon signalling through toll-like receptors, making the peptide relevant well outside infectious disease.
Origin and structure
The 37-residue peptide is released by proteolytic cleavage of hCAP-18, chiefly by proteinase 3 in neutrophils. It adopts an amphipathic helix in membrane-mimetic environments, which is the structural basis for its interaction with bacterial membranes.
Direct killing versus signalling
At higher concentrations LL-37 disrupts microbial membranes directly. At lower, more physiological concentrations it behaves as a signalling molecule, influencing chemotaxis, cytokine release, and wound re-epithelialisation. The two modes are frequently conflated in summaries.
For related mechanism work, see Epitalon telomerase research.
The dual role in inflammation
The peptide can be pro- or anti-inflammatory depending on context and concentration, and it interacts with receptors including FPR2 and P2X7. This context dependence explains why it appears in both inflammatory and resolution-focused literature.
Salt and serum sensitivity
Antimicrobial activity is strongly attenuated by physiological salt and by serum proteins, which is a major reason in vitro potency does not predict in vivo performance. Any assay design must state the ionic conditions.
Autoimmunity connections
LL-37 complexes with self-DNA and self-RNA have been studied in psoriasis and lupus as drivers of interferon signalling through toll-like receptors, making the peptide relevant well outside infectious disease.
Experimental Conditions and Practical Setup
Antimicrobial assays must state ionic strength, because activity drops sharply in physiological saline relative to low-salt buffer. Standard practice is a radial diffusion or broth microdilution assay in low-ionic-strength medium, with a parallel arm in physiological salt to show the magnitude of the effect. Serum inactivation is tested separately by adding a defined percentage of serum.
Conditions that change LL-37 assay outcomes
| Variable | Effect on activity | How to control it |
|---|---|---|
| NaCl concentration | Strongly reduces microbicidal activity | Run parallel low-salt and physiological arms |
| Serum proteins | Bind and neutralise the peptide | State serum percentage explicitly |
| Peptide concentration | Microbicidal versus signalling behaviour | Report molar concentration |
| Aggregation state | Alters membrane interaction | Confirm with light scattering if uncertain |
Practical Notes for the Bench
- Always state ionic strength when reporting antimicrobial assay results.
- Distinguish microbicidal concentrations from immunomodulatory ones.
- Account for serum protein binding when extrapolating from broth assays.
Frequently Asked Questions
Why is it called LL-37?
The name reflects the two N-terminal leucine residues and the 37-residue length of the mature peptide.
Is it only an antibiotic?
No. At lower concentrations it acts mainly as an immunomodulatory and chemotactic signal rather than a direct microbicide.
Why do lab results often fail in vivo?
Physiological salt concentrations and serum binding substantially reduce its antimicrobial potency compared with standard broth assays.
Why does the peptide behave differently at low concentration?
At lower concentrations it acts primarily as a signalling molecule affecting chemotaxis and cytokine release, while direct membrane disruption requires much higher concentrations.
Related Reading
- Epitalon telomerase research
- MOTS-c mitochondrial peptide
- humanin peptide research
- melanocortin peptides
- amylin pramlintide
References & Further Reading
- Fabisiak A et al. LL-37: Cathelicidin-related antimicrobial peptide with pleiotropic activity. Pharmacol Rep. 2016. PubMed 27117377
- Voronko OE et al. Antimicrobial Peptides of the Cathelicidin Family: Focus on LL-37 and Its Modifications. Int J Mol Sci. 2025. PubMed 40869425
- Peptide literature search on PubMed
- Full-text archive at PubMed Central
- USP general chapters on pharmaceutical analysis
The notes below reflect common laboratory practice and open literature. They are not clinical recommendations, and peptides discussed are research materials unless stated otherwise.
Reviewed by Dr. Elena Marchetti, Peptide Chemistry & Analytical Characterization.