LL-37

LL-37 is the only cathelicidin antimicrobial peptide found in humans—a natural-born killer of pathogens that your immune system produces as a first line of defense. The name comes from its structure: 37 amino acids beginning with two leucine residues (LL).

Your body produces LL-37 in immune cells (neutrophils, macrophages), skin cells (keratinocytes), and epithelial barriers (respiratory, gastrointestinal). It's released at infection sites to directly kill invading bacteria, viruses, and fungi while simultaneously signaling the immune system to respond.

Why LL-37 Matters Now

Antibiotic resistance is one of the greatest health threats of our time. Bacteria are evolving faster than we can develop new antibiotics. LL-37 offers a different approach: its membrane-disrupting mechanism is extremely difficult for bacteria to develop resistance to. It can kill MRSA and other superbugs that shrug off conventional antibiotics.

Beyond Killing Pathogens

LL-37 does more than kill microbes. It modulates immune responses, promotes wound healing, disrupts biofilms, and influences inflammation. This multifunctionality makes it relevant to conditions from chronic wounds to inflammatory diseases. It's one of the most studied antimicrobial peptides precisely because its biology is so rich.

LL-37's mechanisms span direct antimicrobial action, immunomodulation, and wound healing.

Direct Pathogen Killing

LL-37 is amphipathic—it has both positively charged and hydrophobic regions. This structure is key. The positive charges attract LL-37 to negatively charged microbial membranes. Once there, the hydrophobic regions insert into the membrane's lipid layer. Multiple LL-37 molecules aggregate, forming pores or destabilizing the membrane. Contents leak out; the microbe dies.

This mechanism works against bacteria (Gram-positive and Gram-negative), enveloped viruses, and fungi. Human cells are protected because our membranes have different composition—more cholesterol, different charge distribution—making them less attractive targets.

Biofilm Disruption

Biofilms protect bacteria from antibiotics and immune attack. LL-37 can prevent biofilm formation, penetrate existing biofilms, and kill bacteria within them. This addresses a major cause of chronic infections.

Immunomodulation

LL-37 influences immune cell behavior—recruiting immune cells to infection sites, modulating inflammatory cytokine production, and affecting how the adaptive immune system responds. This immunomodulatory role explains why LL-37 levels affect susceptibility to various conditions.

Wound Healing

LL-37 promotes wound healing through multiple mechanisms: stimulating cell migration, promoting angiogenesis, and affecting growth factor expression. This wound-healing activity complements its antimicrobial action—killing pathogens while helping tissue repair.

LL-37 has extensive research spanning antimicrobial activity, immunology, and clinical applications.

Antimicrobial Efficacy

Studies confirm LL-37 activity against a wide range of pathogens including antibiotic-resistant strains. Research published in Frontiers in Immunology and elsewhere demonstrates efficacy against MRSA, Pseudomonas, E. coli, Candida, and various viruses.

Biofilm Research

Research in BioMed Research International showed LL-37 disrupts biofilms from multiple bacterial species, with activity against established biofilms—not just prevention of formation.

Clinical Associations

Studies link low LL-37 levels with increased infection susceptibility. Vitamin D's role in LL-37 expression connects vitamin D deficiency to infection risk through this mechanism. Genetic variations affecting LL-37 are associated with disease susceptibility.

Therapeutic Development

Pharmaceutical development of LL-37 and analogs continues, with some compounds in clinical trials for wound infections and other applications.

LL-37 dosing isn't standardized, as it remains a research compound.

Subcutaneous

Dose: 50-200mcg, 1-3 times weekly (varies by protocol)

For: General immune support, systemic effects

Topical

Applied to wounds or skin infections in appropriate formulations.

Considerations

LL-37 is relatively unstable—use freshly reconstituted and store properly. Combination with vitamin D supplementation may enhance natural LL-37 production synergistically.

As an endogenous human peptide, LL-37 has inherent biocompatibility.

Reported Effects

Generally well-tolerated. Injection site reactions possible. At high doses, potential for inflammatory effects (LL-37 is immunoactive).

Considerations

LL-37 has complex roles—beneficial for fighting infection but potentially contributory in some inflammatory conditions (like psoriasis) at high levels. Appropriate dosing is important.