LL-37 — Research, Dosing & Price Guide

LL-37 is the only human cathelicidin antimicrobial peptide — a 37-amino-acid peptide cleaved from the precursor protein hCAP-18 by proteinase 3 in neutrophils. It serves as a critical component of the innate immune system, providing broad-spectrum antimicrobial defense against bacteria, viruses, fungi, and biofilms. Beyond direct killing, LL-37 modulates immune cell recruitment, wound healing, angiogenesis, and inflammation resolution. It is expressed in neutrophils, macrophages, epithelial cells, and keratinocytes, and its deficiency is associated with recurrent infections, chronic wounds, and immune dysfunction. LL-37 is emerging as one of the most important peptides in immunology and infectious disease research.

LL-37 is an amphipathic alpha-helical peptide with a net positive charge (+6 at physiological pH) that underlies its multifaceted biological activities. Its antimicrobial mechanism involves electrostatic attraction to negatively charged bacterial membranes (composed of phosphatidylglycerol and lipopolysaccharide), followed by membrane insertion and disruption. LL-37 can operate through multiple membrane-disruption models: the barrel-stave model (forming transmembrane pores), the toroidal pore model (inducing curvature strain that creates lipidic pores), and the carpet model (coating the membrane surface until a critical concentration causes dissolution). The selectivity for microbial over mammalian cells arises from the fundamental difference in membrane composition — mammalian cell membranes are rich in neutral phosphatidylcholine and cholesterol, which resist LL-37 binding. Beyond direct membrane disruption, LL-37 is a potent anti-biofilm agent. It prevents biofilm formation by Pseudomonas aeruginosa, Staphylococcus aureus (including MRSA), and other biofilm-forming organisms at sub-inhibitory concentrations. It disrupts quorum-sensing signaling, reduces bacterial motility, and downregulates genes essential for biofilm matrix production. This anti-biofilm activity is particularly significant because biofilms are responsible for 80% of chronic infections and are 100–1,000x more resistant to conventional antibiotics. LL-37's immunomodulatory functions are equally important. It serves as an alarmin — signaling danger and recruiting immune cells to sites of infection or tissue damage. It chemoattracts neutrophils, monocytes, and T-cells through formyl peptide receptor-like 1 (FPRL1/FPR2) activation. It promotes macrophage phagocytosis and shifts macrophage polarization from the pro-inflammatory M1 phenotype toward the tissue-repair M2 phenotype, facilitating inflammation resolution. LL-37 neutralizes lipopolysaccharide (LPS/endotoxin) by direct binding, preventing TLR4 activation and the cytokine storm associated with gram-negative sepsis. In wound healing, LL-37 promotes re-epithelialization through EGFR transactivation, stimulates angiogenesis through VEGF induction and direct endothelial cell activation via FPRL1, and increases keratinocyte and fibroblast migration to wound sites. It also promotes wound closure through activation of P2X7 receptors and downstream MAPK signaling. LL-37 has antiviral activity against influenza, HIV, herpes simplex virus, and respiratory syncytial virus — primarily through direct virion disruption and enhancement of antiviral interferon responses. It activates plasmacytoid dendritic cells to produce type I interferons (IFN-α, IFN-β) through TLR9-dependent mechanisms, bridging innate and adaptive antiviral immunity.

• Zanetti (2004) published a comprehensive review in Journal of Leukocyte Biology establishing cathelicidins as multifunctional host defense peptides with antimicrobial, immunomodulatory, and wound-healing properties
• Overhage et al. (2008) demonstrated in Infection and Immunity that LL-37 inhibits Pseudomonas aeruginosa biofilm formation at 0.5 μg/mL — 16x below the MIC — by suppressing quorum sensing and motility genes
• Clinical observations show that individuals with low LL-37 expression (morbus Kostmann patients, vitamin D-deficient individuals) have markedly increased susceptibility to infections, particularly periodontal disease, skin infections, and respiratory infections
• Vitamin D supplementation (which upregulates endogenous LL-37 expression via the vitamin D response element in the cathelicidin gene) reduced respiratory infections by 36% in a meta-analysis of 25 RCTs (BMJ, 2017)
• Research by Lande et al. (2007) in Nature showed LL-37 complexed with self-DNA activates plasmacytoid dendritic cells through TLR9, connecting LL-37 to both antimicrobial defense and autoimmune pathology (psoriasis)
• Studies demonstrated LL-37 neutralizes LPS endotoxin activity, preventing TNF-α release from macrophages and protecting against septic shock in animal models
• Wound healing studies showed LL-37 accelerated re-epithelialization by 30–40% through EGFR transactivation and keratinocyte migration (Journal of Immunology, 2005)
• Anti-MRSA studies showed LL-37 kills methicillin-resistant Staphylococcus aureus at concentrations achievable at wound sites, offering an alternative to failing antibiotics
• Research demonstrated LL-37 has direct antiviral activity against influenza A, disrupting viral envelopes and enhancing interferon-mediated antiviral responses

• Subcutaneous injection for systemic immune support: 50–100 mcg daily or every other day
• Anti-biofilm/chronic infection protocol: 100 mcg subcutaneous daily for 4–8 weeks
• Wound healing: 50–100 mcg injected locally around wound margins, or topical application in a suitable vehicle
• Respiratory infection support: 50–100 mcg subcutaneous daily during acute illness, for 7–14 days
• Oral/sublingual for gut immune support: 100–200 mcg daily
• Cycle: 4–8 weeks on for acute indications; can be used intermittently during infection seasons
• Prophylactic immune support: 50 mcg every other day during cold/flu season
• Can be nebulized for direct respiratory delivery in specific clinical protocols (under medical guidance)
• Start at lower doses (50 mcg) and titrate up based on response and tolerance

Known Side Effects

• Injection site reactions: redness, swelling, warmth, and mild pain (common — LL-37 activates local immune cells, causing a controlled inflammatory response)
• Transient flu-like symptoms possible during first 1–2 days as immune system is activated (low-grade temperature, mild fatigue)
• Mild histamine-like response: flushing, urticaria at injection site (LL-37 activates mast cells)
• Herxheimer-like reaction possible when treating chronic infections or biofilm — temporary worsening of symptoms as microbial die-off releases toxins
• Theoretical concern: LL-37 overexpression is implicated in psoriasis pathogenesis — those with psoriasis should use cautiously
• Rare: nausea with higher doses

Safety Profile

LL-37 is an endogenous human peptide produced naturally by immune cells, epithelial surfaces, and skin — it is a fundamental component of human immunity. Therapeutic administration essentially supplements a system the body already uses. The primary safety consideration is the psoriasis connection: LL-37 forms complexes with self-DNA that can activate autoimmune pathways in genetically susceptible individuals. Those with active psoriasis or a strong family history should exercise caution and discuss with their physician. Otherwise, LL-37 has shown excellent tolerability in research settings. Its antimicrobial selectivity (targeting microbial membranes while sparing mammalian cells) provides an inherent safety margin. Local injection site reactions are expected and indicate immune activation rather than toxicity. Contraindicated in active psoriasis flares, known autoimmune conditions involving LL-37 pathology, and pregnancy (insufficient data). Drug interactions: may synergize with conventional antibiotics (potential to use lower antibiotic doses). Safe for intermittent use for immune support.

Week 1: Injection site may show redness and mild swelling (expected immune activation). Subtle improvements in energy and well-being as immune function is supported. Those with chronic/subclinical infections may experience a Herxheimer-like reaction (temporary symptom flare as microbes are killed). Weeks 2–3: Immune function noticeably improved — fewer cold/flu symptoms if used during infection season. Chronic wounds show improved healing trajectory. Biofilm-associated symptoms (sinus infections, skin infections, gut dysbiosis) begin to improve. Weeks 4–6: Chronic infections show significant improvement. Wound healing is substantially accelerated. Recurrent infection frequency decreases. Systemic inflammation markers may improve. Weeks 7–12: Maximum antimicrobial and immunomodulatory benefits. Chronic biofilm-mediated infections that were previously treatment-resistant may finally resolve. Immune resilience is established. Benefits persist after discontinuation as the immune system has been re-educated and infections cleared, though ongoing immune support may be needed for immunocompromised individuals.

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