LL-37
Cathelicidin antimicrobial peptide LL-37 · Cathelicidin LL-37 · hCAP-18/LL-37 · CAP-18 · CAMP
The only human cathelicidin: broad antimicrobial and biofilm-disrupting innate immune peptide.
Typical dose
250 mcg
once daily
Range
100–500
mcg
Half-life
—
see Dosing
Evidence
Early human
Subcutaneous · Topical · Intranasal
What it is
LL-37 is the only cathelicidin humans make, a 37-residue cationic peptide cleaved from the hCAP-18 precursor and released by neutrophils, keratinocytes and epithelial cells. The name is literal: two leading leucines, 37 residues. In the body it is front-line innate immunity, punching holes in bacterial membranes, neutralising endotoxin, and recruiting immune cells to sites of injury.
It is genuinely broad-spectrum in vitro against Gram-positive and Gram-negative bacteria, some fungi and enveloped viruses, and it disrupts biofilm at concentrations below its killing concentration. That biofilm activity drives most of the interest in it, since chronic sinus, gut and skin infections that survive antibiotic courses often do so inside biofilm.
The caveat matters more here than for most peptides. The only controlled human data is topical, on venous leg ulcers, and the larger of those two trials failed to beat placebo. Injected LL-37 has never been tested in a human trial at all. Community subcutaneous use is extrapolation, and the gap between the concentration that kills microbes and the concentration that is toxic to human cells is narrow.
How it works
LL-37 carries a strong net positive charge of +6 and folds into an amphipathic helix on contact with a membrane. That lets it bind the anionic surface of bacterial membranes preferentially over the more neutral outer leaflet of human cells, then insert, oligomerise and form pores. It kills by lysis rather than by hitting a single enzymatic target, which is why bacterial resistance to it develops slowly.
Beyond killing, it is a signalling molecule. It binds and neutralises LPS, acts through FPR2 and EGFR to recruit neutrophils, monocytes and mast cells, and promotes keratinocyte migration and angiogenesis in wounds. It also directly degranulates mast cells, which explains both the wheal-and-flare people get at injection sites and LL-37's established role in driving rosacea and psoriasis flares.
Dosing
There is no human dosing study for injected LL-37, so every number here is community practice rather than evidence. Start at 100 mcg or lower to gauge the local histamine reaction before going higher.
Reconstitution calculator
Pre-loaded with LL-37’s vial size, water volume and typical dose. Change anything.
Typical: 250 mcg · range 100–500
Draw to
10 u
0.1 mL · 250 mcg
Concentration
2.5 mg/mL
25 mcg per unit
Doses per vial
20
Vial lasts
2 weeks 6 days
Draw to 10 units on the barrel.
Once mixed
Refrigerate at 2-8 C and use within 2-3 weeks; potency falls faster than most peptides because of protease activity and adsorption losses to the vial.
2 mL into a 5 mg vial gives 2.5 mg/mL, so 250 mcg is 0.1 mL, or 10 units on a U-100 syringe. LL-37 is strongly cationic and adsorbs to surfaces, so swirl gently, never shake or vortex, and do not pass it through a syringe filter.
Storage
Before mixing
Stable 12-24 months at -20 C in the sealed vial; keep dry and out of light, since the peptide is hygroscopic.
After mixing
Refrigerate at 2-8 C and use within 2-3 weeks; potency falls faster than most peptides because of protease activity and adsorption losses to the vial.
Reported benefits
- ▪Broad-spectrum in vitro activity against bacteria, fungi and enveloped viruses
- ▪Disrupts biofilm at concentrations below its bactericidal threshold
- ▪Neutralises bacterial LPS, lowering endotoxin-driven inflammation
- ▪Promotes keratinocyte migration and angiogenesis in wound models
- ▪Used anecdotally for chronic sinus, gut and skin problems that resist antibiotics
- ▪Resistance develops slowly because it targets membrane structure, not an enzyme
Side effects
- ▪Marked injection-site reactions: wheal, redness, itch and heat from mast-cell degranulation
- ▪Flushing or transient systemic histamine symptoms at higher doses
- ▪Cytotoxic and haemolytic to human cells at concentrations only modestly above the antimicrobial range
- ▪Can trigger or worsen rosacea, psoriasis and eczema flares
- ▪Pro-angiogenic and tumour-promoting in several cancer models: LL-37 is over-expressed in ovarian and lung cancer and drives proliferation, angiogenesis and metastasis
- ▪Injection-site induration or lumps that persist for several days
- ▪Malaise resembling a die-off reaction if a real bacterial load is being cleared
Do not use if
- ▪Rosacea, psoriasis or atopic dermatitis, where LL-37 is an established disease driver
- ▪Active autoimmune disease, particularly lupus, where LL-37/DNA complexes act as an autoantigen
- ▪Active or recently treated malignancy, particularly ovarian or lung cancer, where LL-37 is over-expressed and promotes tumour growth and angiogenesis
- ▪History of severe histamine reactions or mast cell activation syndrome
- ▪Pregnancy or breastfeeding, where there is no data of any kind
Evidence level — Early human
Small or early-phase human studies only.
Not approved by any regulator; investigational topical formulations reached phase II and the injectable peptide is sold only as a research chemical.
Commonly run with
Thymosin Alpha-1
Thymic peptide that tunes T-cell function; licensed abroad as thymalfasin for hepatitis B.
1600 mcg · 2x weekly, spaced 3-4 days apart
KPV
Tripeptide tail of alpha-MSH used to damp gut and skin inflammation.
500 mcg · 1x daily
BPC-157
Gastric-juice-derived pentadecapeptide studied for tendon, ligament and gut healing.
250 mcg · 1x daily (some split into 2x daily during an acute injury)
LL-37 FAQ
Why does the injection site react so badly?+
LL-37 directly degranulates mast cells, so histamine release at the depot is a pharmacological effect, not an allergy and not a sign of a bad batch. It usually settles over 30-90 minutes. Lowering the dose, diluting further and rotating sites all help; some users take an antihistamine beforehand.
Is LL-37 a replacement for antibiotics?+
No. Everything supporting its antimicrobial effect is in vitro or topical, and the larger randomised trial of topical LL-37 on leg ulcers failed to beat placebo. Treat it as something people try alongside conventional treatment for biofilm-associated problems, not as therapy for an active systemic infection.
Can it be nebulised or used intranasally?+
People do both for sinus and airway complaints, and it is at least plausible since LL-37 is natively an airway peptide. There is no human trial data for either route, and the same cytotoxicity ceiling that applies to any human cell applies to airway epithelium.
How does it compare to KPV?+
KPV is a tripeptide that is purely anti-inflammatory with a very clean side-effect profile. LL-37 actually kills microbes and breaks up biofilm, but at the cost of a much rougher local reaction and a real cytotoxicity ceiling. If the problem is inflammation without an infectious driver, KPV is usually the better fit.
Why does the dose range look so narrow?+
Because the therapeutic window is narrow. The concentrations that lyse bacterial membranes are not far below the concentrations that lyse red blood cells and other human cells. Escalating past the 500 mcg mark buys little extra antimicrobial effect and increases both local and systemic toxicity risk.
References
- 1.Treatment with LL-37 is safe and effective in enhancing healing of hard-to-heal venous leg ulcers: a randomized, placebo-controlled clinical trial — Wound Repair and Regeneration (2014) PMID 25041740
- 2.Evaluation of LL-37 in healing of hard-to-heal venous leg ulcers: A multicentric prospective randomized placebo-controlled clinical trial — Wound Repair and Regeneration (2021) PMID 34687253
- 3.A comprehensive summary of LL-37, the factotum human cathelicidin peptide — Cellular Immunology (2012) PMID 23246832
- 4.Increased serine protease activity and cathelicidin promotes skin inflammation in rosacea — Nature Medicine (2007) PMID 17676051
More immune & inflammation
ARA-290
EPO-derived peptide targeting the innate repair receptor, trialled for small-fibre neuropathy.
2 mg · once daily
Thymosin Alpha-1
Thymic peptide that tunes T-cell function; licensed abroad as thymalfasin for hepatitis B.
1600 mcg · 2x weekly, spaced 3-4 days apart
Thymulin
Zinc-dependent thymic nonapeptide studied for T-cell maturation and inflammatory pain.
250 mcg · once daily