LL-37

Antimicrobial / Immunomodulatory Peptideresearch

Also known as: Cathelicidin, hCAP-18(134-170), Human Cathelicidin Antimicrobial Peptide, CAMP

The only human cathelicidin antimicrobial peptide, a 37-amino acid peptide beginning with two leucines, with broad-spectrum antimicrobial, anti-biofilm, immunomodulatory, and wound healing properties.

Overview

LL-37 is the sole member of the human cathelicidin family of antimicrobial peptides. It is a 37-amino acid peptide that begins with two leucine residues (hence 'LL') and is derived from the C-terminal cleavage of the 18 kDa precursor protein hCAP-18 (human Cationic Antimicrobial Protein-18). LL-37 is produced by neutrophils, macrophages, epithelial cells, and various other cell types as part of the innate immune defense. It possesses direct antimicrobial activity against bacteria (both gram-positive and gram-negative), fungi, viruses, and even some parasites. Beyond direct microbial killing, LL-37 has immunomodulatory functions including chemotaxis of immune cells, modulation of inflammatory responses, anti-biofilm activity, and promotion of wound healing and angiogenesis. Its expression is upregulated by vitamin D, linking vitamin D status to innate immune function. In the biohacking community, LL-37 is used for chronic infections, biofilm-associated conditions (Lyme disease, chronic sinusitis), immune support, and wound healing.

Mechanism of Action

LL-37 exerts its effects through multiple mechanisms: (1) Direct antimicrobial action through disruption of microbial cell membranes — the amphipathic alpha-helical structure inserts into negatively charged bacterial membranes, forming pores and causing lysis; (2) Anti-biofilm activity by disrupting established biofilms and preventing new biofilm formation, including against MRSA, Pseudomonas, and Borrelia; (3) Immunomodulation through activation of formyl peptide receptor-like 1 (FPRL1/FPR2), chemotaxis of neutrophils, monocytes, and T-cells; (4) Neutralization of lipopolysaccharide (LPS/endotoxin), reducing gram-negative bacterial toxicity; (5) Promotion of angiogenesis and wound healing through VEGF upregulation and direct effects on keratinocyte migration; (6) Modulation of adaptive immunity through effects on dendritic cell maturation and T-cell polarization; (7) Antiviral activity through disruption of viral envelopes and interference with viral attachment; (8) Expression is vitamin D-dependent — calcitriol (active vitamin D) directly induces LL-37 gene transcription.

Molecular Formula

C205H340N60O53

Molecular Weight

4493.33 g/mol

Sequence

LLGDFFRKSKEKIGKEFKRIVQRIKDFLRNLVPRTES

Dosage Protocols

Dose Range

50mcg200mcg

Frequency

Once daily

Route

subcutaneous

Cycle Length

2-4 weeks, or as needed during acute illness

Start with lower doses to assess tolerance. LL-37 is a larger peptide and can cause injection site reactions. Some protocols use higher doses (up to 500mcg) but this is less established. Ensure adequate vitamin D status for synergistic effects.

Source: Community protocols and clinical research extrapolation

Side Effects

EffectSeverity
Injection site reactionsmoderate
Flu-like symptomsmild
Fatiguemild
Herxheimer-like reactionsmoderate
Headachemild

Pros & Cons

Broad-spectrum antimicrobial activity against bacteria, fungi, viruses, and biofilms

Unique anti-biofilm properties make it relevant for difficult-to-treat chronic infections

Endogenous human peptide — the body naturally produces and recognizes LL-37

Dual antimicrobial and immunomodulatory activity provides comprehensive immune support

Promotes wound healing and angiogenesis alongside infection control

Limited human clinical trial data for therapeutic use despite extensive basic research

Relatively expensive due to its larger size (37 amino acids) and synthesis complexity

More prominent injection site reactions compared to smaller peptides

At high concentrations, can be cytotoxic to human cells — dose precision is important

Susceptible to proteolytic degradation, potentially limiting bioavailability

Research Studies

Legal Status

Not FDA-approved as a therapeutic. Available as a research chemical. Not specifically scheduled. Research-grade peptide available from specialized suppliers. Quality and purity vary significantly.

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