What is LL-37?
LL-37 gets its name from its structure: it is 37 amino acids long and begins with two leucines, abbreviated L. It is the active piece of a larger protein called hCAP18, the only member of the cathelicidin family in humans. Neutrophils and macrophages make it, and so do the cells lining the skin, airways and gut. Production rises during infection and injury, and vitamin D is one of the signals that switches on the gene behind it.
Cathelicidins belong to a wider group called antimicrobial peptides, or host defense peptides, found in animals, plants and even bacteria. Interest in LL-37 grew as antibiotic resistance became a bigger problem, since peptides that act on microbial membranes work differently from most antibiotics. So far, most of what is known about LL-37 as a possible treatment comes from lab and animal work.
How does LL-37 work?
LL-37 carries a positive charge and folds into a spiral with one water-loving side and one fat-loving side. That lets it stick to the negatively charged surface of many bacteria and disrupt their membranes. In lab studies it also binds bacterial toxins such as lipopolysaccharide and can interfere with biofilms. Beyond killing microbes, it acts as a signal: it attracts immune cells, changes how they respond to infection and has been reported to encourage new blood vessel growth and skin cell migration in wound models.
What has research looked at?
- Bacterial infections and biofilms
- In lab and animal studies, LL-37 and modified versions of it showed activity against a range of bacteria, including some resistant strains and biofilms. Human evidence for treating infections is lacking.
- Chronic wounds
- Small human trials tested LL-37 applied to chronic venous leg ulcers. An early trial reported faster healing, while a larger follow-up found no overall difference, with a possible benefit in larger wounds in an analysis that was not planned in advance.
- Lung and gut infection models
- Mouse studies reported that LL-37, or its mouse counterpart, helped limit some lung and gut infections and the inflammation that came with them.
- Cancer
- Lab and animal research shows a mixed picture. LL-37 appears to promote growth in some tumor types, such as ovarian and breast cancer models, and to suppress it in others, such as some stomach and colon cancer models.
- Vitamin D and immunity
- Studies have linked vitamin D to how much LL-37 the body makes, which is one reason it comes up in research on vitamin D and infection.
Overall, LL-37 is well understood as part of normal immune defense, but evidence for giving it as a treatment is thin. Human data are limited to small wound studies, and much of the infection research uses modified versions of the peptide rather than LL-37 itself.
Side effects and cautions
Because LL-37 is a strong immune signal, more is not simply better. High levels are found in the skin of people with rosacea and psoriasis, and research suggests it can help drive those conditions. It has also been studied in lupus and other autoimmune diseases. At higher concentrations in lab tests, it damages human cells as well as microbes. Anyone with an autoimmune, inflammatory or cancer history should talk to a qualified clinician about any compound that acts on the immune system.
- Local reactions
- It was generally well tolerated in the small wound trials. Outside trials, redness, irritation and swelling where it is applied or injected are described informally.
- Autoimmune disease
- LL-37 can form complexes with the body's own DNA that activate immune cells, a process linked to psoriasis and lupus.
- Rosacea
- Excess LL-37, and abnormal fragments of it, are thought to contribute to the redness and inflammation of rosacea.
- Toxicity to human cells
- In lab studies, higher concentrations damaged red blood cells and other human cells, not only bacteria.
- Tumor effects
- Because it may promote growth of some tumor types in lab models, a cancer history is a reason for extra caution.
Further reading
This page summarizes the research in plain words. To read the studies yourself:
- Published studies on LL-37 PubMed, US National Library of Medicine
- Registered human trials of LL-37 ClinicalTrials.gov
