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Immune

LL-37 (5 mg vial)

Once daily subcutaneous protocol for human cathelicidin antimicrobial peptide research, injected every day for 8 to 12 weeks and optionally extended to 16 weeks.

LL-37, also known as CAP-18, is a 37 amino acid cationic antimicrobial peptide derived from the C-terminal of human cathelicidin (hCAP18). It is the only known human cathelicidin, with broad-spectrum antibacterial activity and immune-modulating properties. This educational protocol presents a once-daily subcutaneous approach with gradual titration and clear insulin-syringe measurements at the reconstitution strength used here.

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Protocol Overview

Concise summary of the regimen.

GoalSupport antimicrobial defense and wound-healing processes.
ScheduleDaily subcutaneous injections for 8 to 12 weeks. The course may be extended to 16 weeks if desired, holding the top titration dose through the extension.
Dose Range50 to 400 mcg daily with gradual titration. The protocol opens at 50 mcg per day and steps up by 50 mcg each week until it reaches 400 mcg per day in week 8.
Reconstitution1.0 mL bacteriostatic water per 5 mg vial (5 mg/mL).
StorageLyophilized frozen; reconstituted refrigerated; avoid repeated freeze-thaw.

Dosing & Reconstitution

WEEKDAILY DOSEUNITS PER INJECTION
Week 150 mcg1 unit
Week 2100 mcg2 units
Week 3150 mcg3 units
Week 4200 mcg4 units
Week 5250 mcg5 units
Week 6300 mcg6 units
Week 7350 mcg7 units
Week 8400 mcg8 units

Frequency is once daily by subcutaneous injection across the whole course. Some protocols instead run five days on and two days off. At 5 mg/mL every dose in this protocol falls between 1 and 8 units, which is well under the 10 unit (0.10 mL) threshold where readability starts to matter, so a 30 unit or 50 unit insulin syringe is the sensible barrel here rather than a 100 unit one. The week 1 dose of 50 mcg is a single unit, which is the smallest reliable draw on that barrel. Sites are rotated systematically across abdomen, thighs, and upper arms to reduce local irritation.

Results Timeline

Sequence described in the research record. Individual response varies.

  • Weeks 1 to 2: opening titration at 50 mcg then 100 mcg daily, 1 unit then 2 units per injection, establishing tolerance and a consistent injection routine.
  • Weeks 3 to 4: 150 mcg then 200 mcg daily, 3 units then 4 units per injection.
  • Weeks 5 to 6: 250 mcg then 300 mcg daily, 5 units then 6 units per injection.
  • Weeks 7 to 8: 350 mcg then 400 mcg daily, 7 units then 8 units per injection. This is where the standard 8 week course ends.
  • Weeks 9 to 16: optional continuation at 400 mcg daily, 8 units per injection, with the same once daily cadence throughout.

Reconstitution Steps

  1. Draw 1.0 mL bacteriostatic water with a sterile syringe.
  2. Inject slowly down the vial wall; avoid foaming.
  3. Gently swirl until dissolved (do not shake).
  4. Label with date and concentration; refrigerate at 2 to 8 °C, protected from light. At 5 mg/mL, 1 unit = 0.01 mL » 50 mcg on a U-100 insulin syringe, so 50 mcg is 1 unit, 200 mcg is 4 units, and 400 mcg is 8 units.

Storage Instructions

Proper storage preserves peptide quality.

  • Lyophilized: store at minus 20 °C in dry, dark conditions; stable for roughly 24 months.
  • Reconstituted: refrigerate at 2 to 8 °C for up to 4 weeks, or freeze at minus 20 °C for up to 6 months.
  • Avoid repeated freeze-thaw cycles, which degrade the peptide; aliquot before freezing if long storage is planned.
  • Allow vials to reach room temperature before opening to reduce condensation uptake, and keep them out of light and heat.

Supplies Needed

Planning math is based on the 8 to 16 week daily protocol with gradual titration from 50 mcg to 400 mcg, which works out to about 1.6 mg per week during the 8 week titration and 2.8 mg per week once the 400 mcg daily dose is held.

Peptide Vials (LL-37, 5 mg vial):

  • An 8 week course totals about 12.6 mg of LL-37, which is 3 vials of 5 mg; a 12 week course totals about 23.8 mg, which is 5 vials, and a 16 week course totals about 35.0 mg, which is 7 vials.

Insulin Syringes (U-100):

  • Per week: 7 U-100 insulin syringes, one per day, with a 30 unit or 50 unit barrel preferred at these small volumes.
  • Full cycle: 56 syringes at 8 weeks, 84 at 12 weeks, and 112 at 16 weeks.

Bacteriostatic Water (10 mL bottles):

  • At 1.0 mL of bacteriostatic water per 5 mg vial, one 10 mL bottle covers 10 vials, so a single bottle covers the full 16 week course.

Alcohol Swabs:

  • Per injection: 2 alcohol swabs, one for the vial stopper and one for the skin, which is 14 per week.
  • Full cycle: 112 swabs at 8 weeks, 168 at 12 weeks, and 224 at 16 weeks, which is three boxes of 100.

Important Notes

Practical considerations for consistency and safety.

  • Use a new sterile insulin syringe for each injection and dispose of it in a sharps container.
  • Rotate injection sites across abdomen, thighs, and upper arms to reduce local irritation.
  • Inject slowly and wait a few seconds before withdrawing the needle.
  • At 5 mg/mL a single vial holds 100 units of solution. During the early titration weeks the daily draw is only 1 to 4 units, so a reconstituted vial can outlast the 4 week refrigerated window and some material is discarded rather than carried on; the vial counts above are built on total mg and allow for that.
  • Document the daily dose and site rotation to maintain consistency across the course.
  • Regulatory Note: LL-37 is not an approved drug for human therapeutic use and is supplied for research purposes only, not for human consumption. The master sheet does not record a WADA classification for this compound.

How This Works

LL-37 exerts both direct and indirect antimicrobial effects. Its amphipathic, cationic alpha-helical structure, with a net charge of plus 6, allows it to preferentially bind and disrupt negatively charged microbial membranes. Beyond direct killing, LL-37 modulates host immunity: in murine sepsis models it induced neutrophils to release microvesicles rich in antimicrobial proteins, lowering bacterial burden and improving survival. LL-37 can also bind bacterial lipopolysaccharide (LPS) and block its interaction with CD14/TLR4, reducing endotoxin-triggered TNF release and neutrophil apoptosis. These combined mechanisms help explain its potential in infection control and tissue repair contexts.

Benefits & Side Effects

Observations from the published record.

  • In chronic venous leg ulcers, which often lack endogenous LL-37, topical treatment with synthetic LL-37 significantly accelerated healing rates compared to placebo.
  • In diabetic foot ulcer trials, LL-37 cream improved granulation tissue formation and wound closure.
  • Broad-spectrum antimicrobial action helps clear infections; in experimental sepsis models, LL-37 treatment reduced bacterial loads and mortality.
  • Immune-modulating effects include binding bacterial LPS and blunting endotoxin-driven TNF release, which is part of the reported benefit in inflammatory settings.
  • Generally well tolerated; occasional mild injection-site reactions such as redness or itch may occur with subcutaneous administration.
  • Much of the supporting clinical evidence is topical rather than subcutaneous, so the injected route described here remains a research context rather than an established therapy.

Lifestyle Factors

Complementary strategies for best outcomes.

  • Optimize vitamin D status, since vitamin D upregulates endogenous cathelicidin and LL-37 expression.
  • Support wound healing with adequate protein intake and micronutrient sufficiency, particularly zinc and vitamin C.
  • Maintain proper wound hygiene and dressing protocols where tissue repair is the goal.
  • Prioritize sleep and stress management to support immune function and recovery.

Injection Technique

General subcutaneous guidance from clinical best-practice resources.

  1. Clean the vial stopper and skin with alcohol; allow to dry.
  2. Pinch a skinfold; insert the needle at 45 to 90 degrees into subcutaneous tissue.
  3. Do not aspirate for subcutaneous injections; inject slowly and steadily.
  4. Wait 5 to 10 seconds before withdrawing; dispose of syringe in sharps container.
  5. Rotate sites systematically (abdomen, thighs, upper arms) to avoid lipohypertrophy.

References

Source citations for further reading.

  1. Evaluation of LL-37 in healing of hard-to-heal venous leg ulcers: multicentric RCT (Wound Repair and Regeneration).
  2. Little peptide, big effects: the role of LL-37 in inflammation and autoimmune disease (Journal of Immunology).
  3. Antimicrobial peptide LL-37 ameliorates a murine sepsis model via microvesicle release (Innate Immunity).
  4. Efficacy of LL-37 cream in enhancing healing of diabetic foot ulcer: RCT (Archives of Dermatological Research).
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Educational and research reference only. Not medical advice. For research use only; not for human consumption.

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