Immune SupportLimited researchantimicrobialbiofilmwound healinginnate immunityinfection

LL-37

Also known as Cathelicidin, CAP-18 fragment, hCAP18 (134-170), Ropocamptide

LL-37 is the only human antimicrobial peptide of the cathelicidin family, a 37 amino acid fragment that white blood cells and skin cells release to kill microbes and break up biofilms. Research is almost entirely in test tubes and animals, with one small topical trial in leg ulcers. Injected LL-37 has essentially no human safety data.

Reviewed by the amino101 editorial team. .

Status
Investigational, not approved anywhere. Treated as prohibited by WADA under S0.
Typical dose
50 to 125 mcg
once daily, or every other day if the injection site reacts
Route
Subcutaneous, Topical
Subcutaneous, belly or thigh, rotating sites; or topical on a wound
Cycle
2 to 6 weeks
Break: 4 weeks or more; there is no safety basis for continuous use
Storage
Fridge 2 to 8 C
fridge 2 to 8 C once mixed, use within 4 weeks; powder in freezer or fridge away from light

Quick start

What people commonly do. Not a prescription.
Typical dose
50 to 125 mcg
How often
once daily, or every other day if the injection site reacts
Where
Subcutaneous, belly or thigh, rotating sites; or topical on a wound
Timing
any time of day, food does not matter
Effects timeline
injection site redness within hours; any wound or infection change is judged over 2 to 4 weeks, and only topical wound use has trial support
Storage
fridge 2 to 8 C once mixed, use within 4 weeks; powder in freezer or fridge away from light
Cycle length
2 to 6 weeks
Break between
4 weeks or more; there is no safety basis for continuous use

A 5 mg vial in 2 mL gives 2.5 mg per mL, so 50 mcg is 2 units and 100 mcg is 4 units on an insulin syringe. Small volumes like this are hard to measure accurately.

Overview

LL-37 is the active fragment of hCAP18, a protein stored in neutrophils and made by skin, gut and airway cells. When tissue is injured or infected, an enzyme cuts hCAP18 to release LL-37, which punches holes in bacterial membranes, breaks up biofilms and signals immune cells to come to the site. It is the only cathelicidin in humans, and its production in skin depends partly on vitamin D. The research market sells a synthetic copy as a general antimicrobial and wound healing peptide, which goes well beyond what the evidence covers.

Human data are thin and need saying up front. The one real trial is a small randomized study of LL-37 applied topically to chronic venous leg ulcers, which found faster healing at the two lower concentrations and no benefit at the highest. A later phase 2b trial of the same topical product, called ropocamptide, reported mixed results with benefit mainly in larger ulcers. Everything else is in vitro or animal work on biofilms, lung infection, wound closure and immune signaling. There are no trials of injected LL-37 in people and no published human safety data for that route.

Community protocols use 50 to 125 mcg daily by subcutaneous injection, or topically on wounds, often for chronic infections, gut dysbiosis or biofilm related complaints. Injected LL-37 causes noticeable injection site inflammation in many people, which fits its biology since it attracts immune cells and can damage host cell membranes at higher concentrations. In 2023 the FDA placed LL-37 in Category 2, closing it to US compounding pharmacies. This page is educational and reports what the research and community use look like, not a treatment plan.

How it works

LL-37 is a cationic amphipathic peptide. Its positive charge attracts it to the negatively charged outer membranes of bacteria, where it inserts and disrupts the membrane, killing Gram positive and Gram negative species as well as some fungi and enveloped viruses. It binds bacterial lipopolysaccharide and neutralizes it, which limits endotoxin driven inflammation. At concentrations below those needed to kill, it stops bacteria attaching to surfaces and breaks down the matrix of established biofilms. On the host side it acts as a chemoattractant for neutrophils, monocytes and T cells through the formyl peptide receptor FPR2, promotes angiogenesis and keratinocyte migration, and shapes cytokine release. The same membrane activity that kills bacteria can damage human cells at higher concentrations, and LL-37 complexed with self DNA is a known driver of inflammation in psoriasis and lupus.

Molecular weight
4493 Da
Length
37 amino acids
Type
Cationic amphipathic alpha helical antimicrobial peptide, C-terminal fragment of hCAP18
Sequence
LLGDFFRKSKEKIGKEFKRIVQRIKDFLRNLVPRTES

Where the research stands

Human trials
Small pilots only
Animal data
Moderate
Safety data
Limited
Regulatory
Not approved anywhere. A topical form reached phase 2 trials for venous leg ulcers. Placed in FDA Category 2 for compounding in 2023.
WADA
Prohibited for athletes
Chronic wound healingEmerging
  • Venous leg ulcers, topical. A small randomized trial found faster healing at low concentrations; a phase 2b follow up was mixed. This is the only human evidence for LL-37.
  • Skin wounds, general. Rodent wound models show faster closure and more blood vessel growth; no human data outside leg ulcers.
Biofilm and chronic infectionWeak or mixed
  • Bacterial biofilms. Strong in vitro data against Pseudomonas and others at sub-killing concentrations; no human trial by any route.
  • Systemic or gut infection. No evidence that injected or oral LL-37 reaches an infection site in useful amounts; it is broken down quickly in serum.
Immune modulationWeak or mixed
  • Innate immune signaling. Well mapped in cell studies, but the same signaling drives autoimmune skin disease, so the direction of any net effect in people is unknown.
Key findings
  • human pilotA randomized, placebo controlled trial of topical LL-37 in 34 patients with chronic venous leg ulcers found significantly faster healing at 0.5 and 1.6 mg per mL, with no benefit at 3.2 mg per mL.
  • in vitroLL-37 at concentrations far below its killing dose prevented Pseudomonas aeruginosa biofilm formation and disrupted established biofilms in culture.
  • in vitroLL-37 complexed with self DNA activated plasmacytoid dendritic cells through TLR9, a mechanism implicated in psoriasis.
  • rodentTopical or gene delivered LL-37 accelerated wound closure and increased vascularization in rodent skin wound models.
  • in vitroLL-37 killed a broad range of Gram positive and Gram negative bacteria and neutralized bacterial lipopolysaccharide in culture.

Rodent and in vitro mean no human data for that finding. Human pilot means small, often uncontrolled. Human RCT means randomized and controlled. Clinical means an approved drug with regulatory data.

Levels over time

Modeled from the half-life. Illustrative, not measured.
Peak
minutes after injection (estimated)
Half-life
minutes to under an hour in plasma; it is rapidly cut by proteases and binds plasma proteins, and no human pharmacokinetic study exists
Cleared
likely within a few hours, though local tissue effects at the injection site persist for a day or more
Repeated dosing every 24 hDose
100%50%dose 11h2h3h5hnext dose at 24h, long after clearance
What this means for dosing

A half-life of 30 min against dosing every 24 h means each dose has cleared before the next. Nothing stacks; you start from zero every time, and the tissue effect is what carries over.

The half-life figure is an estimate from its biology. Serum breaks LL-37 down quickly and binds it to apolipoprotein, which is one reason systemic antimicrobial effect from a subcutaneous dose is doubtful.

LL-37 dosage and protocols

Community runs are short, typically 2 to 6 weeks, partly because injection site reactions accumulate and partly because there is no safety basis for longer use. Starting at 50 mcg and only increasing if the site tolerates it is the usual approach. Topical protocols are applied daily to a cleaned wound for as long as it takes to close. There is no loading or taper.

GoalDoseFrequencyRoute
Starting dose, community50 mcgonce daily for the first weekSubcutaneous, rotating sites
Standard systemic protocol, community100 mcgonce dailySubcutaneous, rotating sites
Higher end125 mcgonce daily or every other daySubcutaneous
Topical wound caredilute solution, about 0.5 to 1.6 mg per mLonce daily to the cleaned woundTopical
Timing

Time of day does not matter. Site rotation matters: injecting the same spot daily compounds the inflammation. The topical concentrations listed come from the leg ulcer trial, which found that the highest concentration tested worked worse than the lower two, so more is not better.

Community protocols report 50 to 125 mcg once daily by subcutaneous injection, starting at the low end because of injection site reactions. Topical use applies a dilute solution directly to a wound. None of this comes from human dosing studies.

Dose calculator

U-100 insulin syringe
Draw
- units
- mL at -
- doses per vial. - per unit.

Units are a volume on the syringe, not an amount of peptide. Concentration changes every time you change the water volume. The standalone calculator explains the math.

Common vial sizes and reconstitution
VialSuggested waterConcentrationLow dose draw
5 mg2 mL2.5 mg/mL2 units
10 mg3 mL3.333 mg/mL1.5 units

How to reconstitute LL-37

  1. 1

    Wash your hands and wipe the work surface. Swab both vial stoppers with alcohol and let them dry.

  2. 2

    Pick the water volume with the calculator above and write it on the vial. The concentration means nothing without it.

  3. 3

    Draw the bacteriostatic water into a mixing syringe.

  4. 4

    Insert at an angle and let the water run down the inside wall. Never squirt it straight onto the powder.

  5. 5

    Swirl gently or leave it to dissolve. Do not shake.

  6. 6

    Label with the date and water volume. Store in the fridge at 2 to 8 C and use within about 4 weeks.

  7. 7

    Unmixed vials keep for months in the fridge and longer in the freezer, sealed and out of light.

  8. Full walkthrough with syringe reading and site rotation: reconstitution guide.
Quality check
  • ✓
    White, fluffy cake

    Lyophilized powder should look like a small white puck or fluffy cake at the bottom of the vial. That is a proper freeze-dry.

  • ✓
    Clear after mixing

    Once dissolved the solution should be water-clear with nothing floating in it.

  • !
    Slight clumping

    Small clumps that dissolve with gentle swirling are fine. Shipping compacts powder.

  • ✕
    Collapsed or melted

    Powder stuck to the sides, glassy, or shrunken means it got hot in transit. Contact the vendor.

  • ✕
    Cloudy or particles

    Persistent cloudiness or visible particles after mixing means degraded or contaminated product. Do not use it.

What to expect
  1. Day 1 to 3

    Redness, warmth, swelling and soreness at the injection site in most people, sometimes a quarter sized or larger welt that takes a day or two to fade.

  2. Week 1 to 2

    Injection site reactions either settle with rotation or get worse; some people report feeling run down or feverish, which is a reason to stop rather than push through.

  3. Week 2 to 6

    Any change in a wound, skin complaint or chronic infection symptom is judged here; for topical wound use this is where the trial measured healing, and for everything else there is nothing to compare against.

Interactions and stacking

Thymosin Alpha-1compatible

Community immune stack; different mechanisms, no known interaction, no trial of the pair.

BPC-157compatible

Used together in wound and gut protocols; no known interaction.

KPVcompatible

KPV is anti-inflammatory and is sometimes added to offset LL-37's inflammatory side; untested as a pair.

TB-500compatible

Appears together in recovery stacks; no known interaction.

Vitamin Dsynergistic

Vitamin D drives the body's own cathelicidin production, so adequate levels are the evidence based way to raise LL-37 in skin and immune cells.

Immunosuppressants and biologicscaution

LL-37 recruits and activates immune cells, which works against immunosuppressive therapy and has not been studied alongside it.

Psoriasis, rosacea or lupus treatmentavoid

LL-37 is a recognized driver of inflammation in these conditions; adding more of it is a bad idea.

Safety

Side effects and cautions
  • ▲Injection site redness, swelling, warmth and pain, often significant
  • ▲Welts or firm lumps at injection sites that last days
  • ▲Fatigue or a flu like feeling after doses
  • ▲Low grade fever or chills
  • ▲Itching or rash near the injection site
  • ▲Worsening of existing inflammatory skin conditions
  • ▲Injected LL-37 has essentially no human safety data. The only human trial was topical, on open ulcers, at low concentrations.
  • ▲Injection site inflammation, redness and pain are common and can be significant. This is expected from a peptide whose job is to attract immune cells and disrupt membranes.
  • ▲LL-37 is implicated in psoriasis, rosacea and lupus as a driver of autoimmune inflammation. Anyone with those conditions has a specific reason to avoid it.
  • ▲At higher concentrations it damages human cells, not just bacteria. The leg ulcer trial lost its benefit at the highest dose.
  • ▲In 2023 the FDA placed LL-37 in Category 2, so it cannot be compounded in the US.
  • ▲Treated as prohibited in sport by WADA under S0.
Stop and reassess if
  • ■Injection site reactions spread, blister, ulcerate or do not settle within a few days
  • ■Fever, chills or a flu like illness after doses
  • ■Any flare of psoriasis, rosacea, eczema or a known autoimmune condition
  • ■Signs of an allergic reaction such as hives, swelling or trouble breathing
  • ■Joint pain, unusual fatigue or other new symptoms that suggest a systemic inflammatory response
Educational only. Dose ranges describe what appears in published research and community protocols. This is not medical advice and most of these compounds are not approved for human use. Talk to a clinician who knows your history.

Community poll

Self-reported by visitors. Not clinical evidence.
What is your experience with LL-37?
If you have used it, how well did it work for you?
Any side effects?
Where did you first hear about it?

LL-37: frequently asked

What LL-37 dosage do community protocols use?

Reported protocols run 50 to 125 mcg once daily by subcutaneous injection, usually starting at 50 mcg to see how the injection site reacts. Topical protocols dilute it in saline or a carrier and apply to the wound. No human study has tested any injected dosage, so these numbers come from vendors and forums rather than research.

Why does LL-37 cause so much injection site reaction?

Because that is what it does in the body. LL-37 recruits neutrophils and monocytes to wherever it is released, promotes local inflammation and can disrupt host cell membranes at higher concentrations. Injecting a bolus under the skin creates exactly the signal that pulls immune cells to the site. Redness, warmth, swelling and pain for a day or two are commonly reported.

Does LL-37 work against biofilms in people?

In culture, yes, at low concentrations against several bacteria. In people, nobody knows. The in vitro biofilm work is real but no human trial has tested LL-37 against a biofilm infection by any route. Community use for chronic sinus, gut or Lyme related complaints rests entirely on the test tube data.

Is LL-37 safe if the body already makes it?

The body makes it in controlled amounts at specific sites, cleaved from a precursor on demand. That is different from injecting a fixed dose under the skin. Natural LL-37 at the wrong place or in excess is linked to psoriasis, rosacea and lupus, so endogenous does not mean harmless.

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
  2. Human host defense peptide LL-37 prevents bacterial biofilm formation. Infection and Immunity, 2008
  3. LL-37, the only human member of the cathelicidin family of antimicrobial peptides. Biochimica et Biophysica Acta, 2006
  4. Plasmacytoid dendritic cells sense self-DNA coupled with antimicrobial peptide. Nature, 2007