COMPOUND

Compounds / Immune

LL-37

Cathelicidin LL-37 (hCAP-18 cleavage product)

Immune SubQ · Topical Not FDA approved

37-amino-acid C-terminal cleavage product of human cathelicidin precursor hCAP-18, the only cathelicidin in humans. Endogenous antimicrobial peptide produced by neutrophils, epithelial cells, and macrophages. Synthetic LL-37 is used for chronic biofilm infections (Lyme, dental, sinus), antimicrobial-resistant skin infections, and immune modulation.

At a glance

Routes
SubQ · Topical
Vial sizes
1 mg · 5 mg
Evidence base
4 studies 4 review

Mechanism

Amphipathic peptide that inserts into and disrupts negatively charged microbial membranes, effective against gram-positive, gram-negative, mycobacteria, fungi, and several enveloped viruses. Disrupts established bacterial biofilms (relevant for chronic infections where planktonic-phase antibiotics fail). Beyond antimicrobial action, LL-37 is a potent immune modulator: chemoattractant via FPRL-1, promotes wound closure via EGFR transactivation, modulates apoptosis and angiogenesis. Dual role as TLR agonist or antagonist depending on cellular context. At supraphysiologic concentrations LL-37 is cytotoxic to host cells and is implicated as a driver in psoriasis and rosacea pathogenesis.

Dosing

No standardized human dosing has been established. Every catalogued study for LL-37 is preclinical or a literature review. Amounts used in animal models do not translate directly to humans.

Published evidence

  1. Review 2020

    Cathelicidins Modulate TLR-Activation and Inflammation

    Scheenstra MR, van Harten RM, Veldhuizen EJA, Haagsman HP, Coorens M Front Immunol

    Dual role: neutralizes bacterial endotoxin (anti-inflammatory) but synergizes with self-DNA to activate TLR9 (pro-inflammatory in autoimmunity).

    PMID 32849591

  2. Review 2012

    A comprehensive summary of LL-37, the factotum human cathelicidin peptide

    Vandamme D, Landuyt B, Luyten W, Schoofs L Cell Immunol

    Comprehensive immunomodulatory + antimicrobial review. Maps the broad receptor / pathway footprint (FPRL-1, P2X7, EGFR, TLR9 modulation in psoriasis).

    PMID 23246832

  3. Review 2012

    Cathelicidin LL-37: an antimicrobial peptide with a role in inflammatory skin disease

    Reinholz M, Ruzicka T, Schauber J Ann Dermatol

    Implicates excessive LL-37 production in rosacea pathogenesis. Counter-evidence to indiscriminate LL-37 supplementation.

    PMID 22577261

  4. Review 2006

    LL-37, the only human member of the cathelicidin family of antimicrobial peptides

    Dürr UH, Sudheendra US, Ramamoorthy A Biochim Biophys Acta

    Foundational structure-function review. Defines amphipathic α-helical structure, membrane-disruption mechanism, dose-dependent cytotoxicity to host cells, antimicrobial spectrum.

    PMID 16716248

Reported side effects

Injection site reaction
Occasional Mild · Mild burning / redness at SC site: LL-37 is amphipathic and can disrupt local cell membranes transiently.
Flu-like symptoms / cytokine release
Occasional Moderate · First-dose flu-like reactions (chills, malaise, low-grade fever) reported, especially with >300 mcg or in users with chronic biofilm infections (Herxheimer-style).
Pro-inflammatory effects in autoimmune conditions
Theoretical Moderate · Elevated endogenous LL-37 is implicated in rosacea (PMID 22577261) and psoriasis (LL-37 + self-DNA forms a TLR9 ligand activating plasmacytoid dendritic cells). AVOID in users with active psoriasis, rosacea, or lupus.
Hemolysis at high concentrations
Rare Serious · In vitro hemolytic at >25-50 µM. IV bolus contraindicated. SC at typical research doses should not reach hemolytic plasma levels but monitor in chronic users.
Long-term safety unknown
Unknown Mild · No human chronic-use safety database for synthetic LL-37 administration.

Interactions

  • Thymosin Alpha-1 Synergy

    LL-37 (innate immune activator + direct antimicrobial) + TA-1 (adaptive immune restoration via TLR-9 / DC-T-cell axis) is a complementary immune stack for chronic infection.

  • BPC-157 Synergy

    LL-37 anti-microbial + immunomodulatory; BPC-157 angiogenesis + epithelial repair. Common pairing for chronic wound / biofilm protocols.

Reconstitution and storage

5 mg vial + 2 mL BAC water = 2.5 mg/mL = 250 mcg per 0.1 mL (10 units on insulin syringe). Highly amphipathic. Handle gently to avoid foaming. Do not shake.

Lyophilized: freezer (-20°C). Reconstituted: refrigerate 2-8°C, use within 14-21 days (LL-37 is more protease-sensitive than most research peptides, shorter than typical 28-day post-recon window).

Open the reconstitution calculator for LL-37