LL-37

LL-37 is the cleaved active form of hCAP18, produced by neutrophils and epithelial cells and induced by vitamin D. Its antimicrobial action is physical - the positively charged helix inserts into negatively charged bacterial membranes - which is why resistance to it is uncommon, and it has documented activity against established biofilms including Pseudomonas. Its immunomodulatory side is more complicated: it neutralises LPS, recruits neutrophils and monocytes via the formyl peptide receptor FPRL1, transactivates EGFR to drive keratinocyte migration, and induces VEGF for angiogenesis. It cuts both ways, though - LL-37 is overexpressed in rosacea and forms immunostimulatory complexes with self-DNA in psoriasis, so it is a driver of those diseases rather than a treatment for them.

Targets: Bacterial membranes and biofilms, FPRL1 / formyl peptide receptor-like 1, EGFR transactivation, LPS neutralisation, VEGF-driven angiogenesis

• · There is no validated human systemic dose. This band is what the research-peptide community converged on, and it is generally run for short periods because LL-37 is genuinely pro-inflammatory at higher exposures.
• · The venous leg ulcer trial applied LL-37 at 0.5 and 1.6 mg/mL twice weekly for four weeks; the lower concentrations outperformed the highest one, which is a useful reminder that more is not better with this peptide.

Work out your exact syringe units →

• very commonInjection-site redness, itching and wheal— LL-37 directly degranulates mast cells, so a local histamine reaction is expected rather than allergic.
• commonFlushing and itching
• uncommonFlu-like malaise
• uncommonFlare of rosacea or psoriasis— Mechanistically expected - LL-37 is implicated in the pathogenesis of both conditions.

• Rosacea or psoriasis - LL-37 is part of the disease mechanism in both, and exogenous dosing can reasonably be expected to make them worse.
• Mast cell activation syndrome or severe histamine intolerance - direct mast cell degranulation is one of its documented actions.
• Active autoimmune disease driven by anti-DNA responses, such as lupus - LL-37/DNA complexes are a known immunostimulatory trigger.

• synergyAntihistamines — Often taken before dosing specifically to blunt the local and systemic histamine response.
• synergybpc-157 — Stacked for infected or slow-healing wounds - antimicrobial plus angiogenic.

• · Watch skin closely, particularly if you have any inflammatory dermatosis history.
• · No established bloodwork.

Not approved for human use anywhere; sold as a research chemical. In April 2026 the FDA removed LL-37 from the Category 2 bulk drug substances list, alongside BPC-157, TB-500 and KPV. Removal from Category 2 is not authorisation to compound - LL-37 was not among the peptides taken to the July 2026 Pharmacy Compounding Advisory Committee vote, so it has no affirmative 503A listing.

• Grönberg et al. 2014, treatment with LL-37 is safe and effective in venous leg ulcers, Wound Repair and Regeneration (trial)
• Vandamme et al., a comprehensive summary of LL-37, the factotum human cathelicidin peptide (review) (review)
• Lande et al., LL-37 and self-DNA complexes as a psoriasis trigger, Nature (preclinical)

LL-37 has two mechanisms that pull in opposite directions, and understanding that is the whole point of this entry. The antimicrobial mechanism is physical. The peptide is strongly cationic and, on contact with the anionic phospholipids of a bacterial membrane, folds into an amphipathic helix and inserts. That disrupts membrane integrity directly. Because the target is a bulk membrane property rather than a protein, resistance is uncommon and slow to develop, and the same property lets LL-37 penetrate established biofilms - including Pseudomonas biofilms, which is a genuinely hard problem. Mammalian membranes are more cholesterol-rich and less anionic, which is what provides the selectivity, but the margin is not enormous, which is why high local concentrations irritate. The repair mechanism runs through receptors. LL-37 signals at FPRL1 (formyl peptide receptor-like 1, also called FPR2) to recruit neutrophils and monocytes, transactivates EGFR to drive keratinocyte migration and re-epithelialisation, induces VEGF for angiogenesis, and neutralises LPS, blunting endotoxin-driven inflammation. And then the third arm, which is why this compound is not a general-purpose anti-inflammatory: LL-37 degranulates mast cells directly, and it complexes with self-DNA to form structures that activate plasmacytoid dendritic cells through TLR9. That second finding is the mechanism by which LL-37 breaks tolerance to self-DNA in psoriasis - it is a driver of the disease, not a treatment for it. LL-37 is also overexpressed in rosacea lesional skin. So the clinical shape is: useful topically on an infected or stalled wound at low concentration, and progressively counterproductive as concentration and duration rise. The venous leg ulcer trial demonstrated this beautifully. Healing rate constants at 0.5 and 1.6 mg/mL were roughly six-fold and three-fold higher than placebo. The 3.2 mg/mL arm showed no benefit over placebo at all. More is not better with this peptide, and the dose-response is not just flat at the top - it inverts.

The dose-response inverts, and people do not expect that. In the only randomised human trial, the two lower concentrations produced roughly six-fold and three-fold faster healing while the highest concentration did nothing at all. If you are used to peptides where more is neutral, this one punishes escalation. The second problem is that the wheal, itch and flushing look like an allergic reaction and are not - LL-37 degranulates mast cells directly, so this is on-target pharmacology. That means antihistamines blunt it, which then encourages people to dose higher than their tolerance would otherwise allow. The third is running it in the wrong skin. Rosacea and psoriasis both involve LL-37 as part of the disease mechanism. Injecting it into someone with either is not an unlucky side effect, it is a predictable flare, and the psoriasis mechanism is documented at the level of a Nature paper. The fourth is adsorption losses. LL-37 sticks to glass and plastic. You will lose peptide to the vial and syringe, apparent potency will be lower than the label suggests, and the wrong response to that is escalating into the inverted part of the dose-response curve. The fifth is running it long. Sustained elevated LL-37 is a feature of inflammatory skin disease, not of healthy tissue. Two to four weeks, then stop.

1. 100 mcgDays 1-3 — Start at the bottom of the range. Histamine-type reactions are dose-related and appear within minutes, so you find out quickly. Some people pre-dose an antihistamine specifically to blunt this; that is common practice but it also masks the signal you are titrating against.
2. 200 mcgDays 4-10 — Only step up if the wheal and flushing from step 1 settled within an hour or two. A large persistent local reaction means you are already at your ceiling.
3. 300 mcgDays 11-28 — The top of the community range. There is no validated human systemic dose at any point on this ladder - this is what the research-peptide community converged on, not a trial-derived schedule.
4. —After week 4 — Stop. Sustained elevation of LL-37 is associated with inflammatory skin disease rather than with repair, and the leg ulcer trial showed the highest concentration performing no better than placebo. Both facts point the same way: short courses only.

• Bacterial membranes and biofilms — Not a receptor - electrostatic attraction to anionic phospholipids followed by helical insertion

  Direct membrane disruption with broad-spectrum activity and documented penetration of established biofilms. Resistance is uncommon because the target is a bulk membrane property.

• FPRL1 / FPR2 (formyl peptide receptor-like 1) — The principal identified receptor for LL-37 on immune cells; binding constants not stated here

  Chemotaxis of neutrophils, monocytes and T cells into the wound. Pro-inflammatory recruitment, which is useful in a stalled wound and unhelpful in inflamed skin.

• EGFR (transactivation) — Indirect, via metalloproteinase-mediated shedding of EGFR ligands

  Keratinocyte migration and re-epithelialisation - the mechanism most directly responsible for the wound-closure effect.

• Lipopolysaccharide (LPS) — Direct binding and neutralisation

  Blunts endotoxin-driven inflammatory signalling, which is part of why it calms an infected wound rather than only sterilising it.

• Mast cells — Direct degranulation, receptor-mediated

  Histamine release. This is the mechanism of the injection-site wheal and itch, and it is expected pharmacology rather than an allergic reaction.

• TLR9 via LL-37/self-DNA complexes — The complex, not the peptide alone, is the ligand

  Activates plasmacytoid dendritic cells and drives interferon-alpha production. This is a described mechanism of psoriasis pathogenesis and the single strongest reason not to run LL-37 in anyone with an inflammatory dermatosis.

• Randomised double-blind dose-response trial of topical LL-37 in hard-to-heal venous leg ulcers Phase 2 (dose-response) · n=34 · 11 weeks · 2014

  34 patients, with a three-week open-label placebo run-in, then a four-week randomised double-blind phase with twice-weekly application of LL-37 at 0.5, 1.6 or 3.2 mg/mL versus placebo, then four weeks of follow-up. Healing rate constants at 0.5 and 1.6 mg/mL were approximately six-fold and three-fold higher than placebo, with mean ulcer area reductions of 68 percent and 50 percent. The highest concentration showed no benefit over placebo. Safe and well tolerated.

Minutes: wheal, redness and itch at the injection site, sometimes with flushing. Expected, dose-related, and your titration signal. Days 1-3: flu-like malaise in some people at the higher end of dosing. Weeks 1-2: topical wound effects were measurable in this window in the leg ulcer trial, with twice-weekly application. Weeks 2-4: the extent of a sensible course. Systemic anecdotal use is judged here, and this is also where you stop. Beyond four weeks: no data, and a mechanistic reason to expect the balance to shift from repair toward inflammation.

The pairing people actually use is an antihistamine taken before dosing, specifically to blunt the mast cell response. It works, and it also removes the feedback you would otherwise use to find your dose. If you are going to do it, establish your tolerance without the antihistamine first. With BPC-157 for an infected or stalled wound the logic is sound - antimicrobial and re-epithelialising from LL-37, angiogenesis from BPC-157. That is one of the better-reasoned stacks in this class for a specific problem rather than a general one. With vitamin D there is a real and under-appreciated relationship: the cathelicidin gene carries a vitamin D response element, so vitamin D status directly governs how much LL-37 you make yourself. Correcting a deficiency is a legitimate alternative to buying the peptide, not just an adjunct to it. With anything else in a long stack, the caution is duration. LL-37 is the compound in this class least suited to being a background component of a permanent protocol.

Against topical antibiotics for an infected wound: LL-37 has the unusual advantage of biofilm penetration and a low resistance risk, which is exactly where conventional antibiotics struggle. It also has one small randomised trial versus decades of data for the alternatives. Against BPC-157 and TB-500 for wound healing: those act on perfusion and cell migration and have no antimicrobial activity at all. LL-37 is the only compound in this class that addresses bacterial burden, which is the actual reason many chronic wounds do not close. Against systemic use of any of the above: LL-37 is the one where the evidence is topical and the systemic use is the extrapolation - the reverse of the usual pattern in this class, and worth noticing. Against fixing vitamin D status: if your 25-hydroxyvitamin D is low, you are underproducing your own cathelicidin, and correcting that costs almost nothing and carries none of the mast cell or psoriasis risk. Do that first.

$40–$130/month. Order-of-magnitude estimate for research-chemical vials at 100-300 mcg daily over a short course. Adsorption losses to glass and plastic mean effective cost per delivered microgram is higher than the label implies. Not price-checked in the preparation of this entry.

• ?No pharmacokinetic parameters exist for exogenous LL-37 in humans by any route - no tmax, bioavailability, volume of distribution, protein binding or clearance figure.
• ?The 100-300 mcg daily subcutaneous band is community convention with no trial behind it. The only human dosing data is topical and expressed as a concentration, not a systemic dose.
• ?How much peptide is lost to adsorption on glass and plastic in practice is unquantified, so delivered dose is uncertain.
• ?The relative contribution of LL-37 fragments such as KS-30 and RK-31 after exogenous dosing has not been characterised.
• ?Whether the inverted dose-response seen topically also applies to systemic dosing is unknown but plausible.
• ?Long-term systemic safety is entirely uncharacterised, and the mechanistic reasons for concern are specific rather than generic.
• ?Cost figures are estimates and were not price-verified in this session.

• Treatment with LL-37 is safe and effective in enhancing healing of hard-to-heal venous leg ulcers: a randomized placebo-controlled clinical trial Grönberg A, Mahlapuu M, Ståhle M, Whately-Smith C, Rollman O, Wound Repair and Regeneration, 2014 · PMID 25041740

  The only randomised human efficacy trial of LL-37, and the source of the crucial finding that the highest concentration did not beat placebo.

• A comprehensive summary of LL-37, the factotum human cathelicidin peptide Vandamme D, Landuyt B, Luyten W, Schoofs L, Cellular Immunology, 2012 · PMID 23246832

  The best single overview of how many contradictory things this peptide does, including the receptor pharmacology and the fragment biology.

• Plasmacytoid dendritic cells sense self-DNA coupled with antimicrobial peptide Lande R et al., Nature, 2007 · PMID 17873860

  The paper establishing LL-37/self-DNA complexes as a driver of psoriasis. This is the citation behind the contraindication, and it is a strong one.