What is LL-37?

LL-37, also known as cathelicidin antimicrobial peptide (CAMP), is a naturally occurring 37-amino-acid peptide derived from the human cathelicidin precursor protein hCAP18. Its sequence is Leu-Leu-Gly-Asp-Phe-Phe-Arg-Lys-Ser-Lys-Glu-Lys-Ile-Gly-Lys-Glu-Phe-Lys-Arg-Ile-Val-Gln-Arg-Ile-Lys-Asp-Phe-Leu-Arg-Asn-Leu-Val-Pro-Arg-Thr-Glu-Ser, with a molecular weight of approximately 4493.3 g/mol. LL-37 is a water-soluble, cationic, amphipathic peptide featuring an alpha-helical structure, produced by neutrophils, epithelial cells, and other immune cells. It is activated by cleavage from hCAP18 by enzymes like proteinase 3. Synthetic LL-37 is typically administered via subcutaneous injection (e.g., 100-300 mcg/day), topical application, or intravenous infusion in research settings. LL-37 is under investigation for its antimicrobial, immunomodulatory, and wound-healing properties, available as a research chemical or through specialized protocols, with potential therapeutic development hindered by cost and stability challenges.

Mechanism of Action

LL-37’s primary mechanism involves fighting infections, modulating immunity, and promoting tissue repair, through the following processes:

Antimicrobial Activity: LL-37 disrupts microbial membranes via electrostatic interaction with negatively charged bacterial, fungal, or viral surfaces, forming pores and causing lysis, effective against Gram-positive, Gram-negative, and enveloped viruses.

Immune Modulation: It acts as a chemoattractant, recruiting immune cells (e.g., monocytes, neutrophils, T-cells) via formyl peptide receptor-like 1 (FPRL1), enhancing innate immunity while also dampening excessive inflammation.

Anti-Inflammatory Effects: LL-37 inhibits pro-inflammatory responses by neutralizing lipopolysaccharides (LPS) from Gram-negative bacteria, reducing TLR4 signaling and cytokine release (e.g., TNF-α, IL-6).

Wound Healing Promotion: It stimulates angiogenesis, keratinocyte proliferation, and migration via EGFR and FPRL1 pathways, accelerating tissue repair and re-epithelialization.

Biofilm Disruption: LL-37 prevents biofilm formation and disperses existing biofilms, enhancing antibiotic efficacy against resistant pathogens.

Antiviral Activity: It binds to viral envelopes (e.g., HIV, HSV) and disrupts viral entry, offering broad-spectrum antiviral effects in preclinical models.

LL-37’s dual role in amplifying innate immunity while curbing excessive inflammation distinguishes it as a versatile host-defense peptide.

Benefits

LL-37’s benefits, supported by preclinical and limited clinical studies, include:

Infection Resistance: Kills a wide range of pathogens, including antibiotic-resistant strains (e.g., MRSA, Pseudomonas aeruginosa), reducing infection risk.

Immune Balance: Enhances innate immunity while preventing sepsis-like inflammatory overreactions, aiding in chronic infections or wounds.

Wound Healing: Accelerates skin and mucosal repair, reducing scarring and infection in burns, ulcers, or surgical wounds.

Anti-Inflammatory Action: Mitigates chronic inflammation in conditions like psoriasis or IBD, balancing immune responses.

Antiviral Protection: Offers potential defense against viral infections, including influenza and herpesviruses.

Biofilm Control: Improves outcomes in chronic infections by disrupting biofilms, enhancing antibiotic penetration.

These benefits highlight LL-37’s potential as a broad-spectrum therapeutic for infection, inflammation, and repair.

Use Cases

LL-37 is primarily experimental, with applications including:

Bacterial Infections: Investigated for antibiotic-resistant infections (e.g., MRSA, P. aeruginosa) via topical or systemic administration (e.g., 100-300 mcg/day).

Wound Healing: Used in preclinical models and off-label for burns, diabetic ulcers, or surgical wounds (e.g., topical gels).

Inflammatory Diseases: Explored for psoriasis, IBD, and rosacea (e.g., 50-200 mcg/day topical or SC) to reduce inflammation.

Viral Infections: Studied for potential in HIV, HSV, or influenza models (e.g., 5-10 mg/kg in mice) to disrupt viral entry.

Biofilm-Related Conditions: Applied in research for chronic infections like cystic fibrosis or implant infections (e.g., combined with antibiotics).

Administration varies from topical applications to subcutaneous or IV routes, with dosing tailored to research or anecdotal use.

Research Studies

Below is a summary of key studies on LL-37, focusing on its mechanisms and benefits:

Zanetti et al. (1995) - Journal of Biological Chemistry Identified LL-37 as the active antimicrobial fragment of hCAP18, effective against E. coli and S. aureus in vitro.

Bals et al. (1998) - Journal of Clinical Investigation Showed LL-37 (10 µM) enhances bacterial clearance and reduces inflammation in P. aeruginosa-infected mice lungs.

Nijnik et al. (2011) - Nature Reviews Immunology Reported LL-37 acts as an immune modulator, recruiting monocytes and balancing cytokine responses via FPRL1.

Scott et al. (2002) - Journal of Immunology Demonstrated LL-37 (20 µg/mL) neutralizes LPS and reduces TNF-α in macrophages, preventing endotoxic shock.

Steinstraesser et al. (2011) - Journal of Investigative Dermatology Found LL-37 (10 µg/mL) accelerates wound closure and angiogenesis in human skin models.

Overhage et al. (2008) - Infection and Immunity Indicated LL-37 (10 µg/mL) disrupts P. aeruginosa biofilms, enhancing antibiotic efficacy in vitro.

Shai et al. (2006) - Current Protein & Peptide Science Showed LL-37 (5 µM) inhibits HIV and HSV entry in cell cultures, offering antiviral potential.

These studies underscore LL-37’s promise, though clinical translation remains limited.

Considerations

Safety: Generally well-tolerated in preclinical models, with potential cytotoxicity at high doses (e.g., >50 µM); human side effects are understudied but may include mild irritation.

Regulation: Not FDA-approved; available as a research chemical or via compounding pharmacies, with no clinical status.

Evidence: Strong preclinical support for antimicrobial and healing effects; human data are sparse, requiring clinical trials for validation.

In conclusion, LL-37 is a naturally occurring peptide with synthetic applications, showing significant potential to fight infections, modulate immunity, and promote healing by targeting microbial and immune pathways. Its efficacy in preclinical studies is promising, but limited human data necessitate further research to establish its therapeutic role.

Why Choose Protide Health?
✅ Lab-Verified Purity (99%) – Third-party tested to confirm quality and consistency.
✅ Research-Informed Development – Formulated with insights from the latest studies on cognitive health, neuroprotection, and mental performance.

For Research Use Only. Not For Human Consumption.