LL-37
Evidence: B — Meaningful Human EvidenceAnti-inflammatory / gut / skin research
Key facts
- Research areaAnti-inflammatory / gut / skin research
- Study records148 human
- Study-at-a-Glance1published summaries
- Last updated2026-07-30
Evidence Snapshot
What this grade covers
A for identity; B/C for selected topical wound studies; D/E for systemic infection treatment, immune boosting, generalized wound healing, approval, safety, or dosing.
Regulatory Context
Endogenous human host-defense peptide studied experimentally; no FDA-approved systemic LL-37 medicine was identified.
In Plain English
A quick, research-focused overview. It does not replace, and cannot outrank, the detailed evidence below.
What is it?
LL-37 is the 37-amino-acid active human cathelicidin host-defense peptide. Human topical wound trials have evaluated LL-37 formulations, while mechanistic research shows antimicrobial, wound-healing, and context-dependent inflammatory activity. These topical data do not establish safety or efficacy for systemic or injectable use.
Why are researchers interested in it?
LL-37 is a cationic, amphipathic host-defense peptide generated from the hCAP18 precursor. It can disrupt microbial membranes and also modulate chemotaxis, cytokine signaling, cell migration, angiogenesis, and nucleic-acid sensing. Its effects are context-dependent: the same peptide can support wound responses while contributing to inflammatory pathways such as psoriasis.
What does the evidence look like?
Evidence grade B/C. Evidence types and limitations are separated below.
Biggest things to know
Topical wound-trial data cannot be generalized to systemic or injectable use.
Research Takeaway
LL-37 is the 37-amino-acid human cathelicidin peptide generated from the hCAP18 precursor; evidence for full-length hCAP18, rodent CRAMP, scrambled controls, shortened analogs, or proprietary LL-37 derivatives must be kept separate.
Evidence boundary: Endogenous peptide biology and the evidence for a manufactured therapeutic preparation are related but not interchangeable.
See all 6 evidence claims →Quick Summary
LL-37 is the 37-amino-acid active human cathelicidin host-defense peptide. Human topical wound trials have evaluated LL-37 formulations, while mechanistic research shows antimicrobial, wound-healing, and context-dependent inflammatory activity. These topical data do not establish safety or efficacy for systemic or injectable use.
Mechanism & Research Overview
LL-37 is a cationic, amphipathic host-defense peptide generated from the hCAP18 precursor. It can disrupt microbial membranes and also modulate chemotaxis, cytokine signaling, cell migration, angiogenesis, and nucleic-acid sensing. Its effects are context-dependent: the same peptide can support wound responses while contributing to inflammatory pathways such as psoriasis.
Mechanism pathway
Relationship-support labels describe the type and directness of the research available, not proof of safety or effectiveness. Indirectly supported, inferred and uncertain relationships are not equivalent to directly supported ones.
- CompoundLL-37
- Supported indirectly (Indirectly supported relationship)Biological targetImmune/keratinocyte signalingOther Defined Target
- Leads toPathwayImmune & Inflammatory Signaling
Relationship details
- LL-37 → Immune/keratinocyte signaling — Supported indirectlyContext-dependent immunomodulatory and keratinocyte-survival effects.
Relevant tissue/system context: Keratinocytes; innate immune cells
Evidence Claims
Individual scientific statements drawn from the sources cited below, each shown with the specific evidence boundary that statement does not establish.
Supported
LL-37 is the 37-amino-acid human cathelicidin peptide generated from the hCAP18 precursor; evidence for full-length hCAP18, rodent CRAMP, scrambled controls, shortened analogs, or proprietary LL-37 derivatives must be kept separate.
Does not establish
Evidence boundary: Endogenous peptide biology and the evidence for a manufactured therapeutic preparation are related but not interchangeable.
Supported
LL-37 has antimicrobial and immunomodulatory functions and also influences keratinocyte and wound-healing biology, but its immune effects are context-dependent rather than uniformly stimulatory.
Does not establish
Evidence boundary: Broad descriptions such as "immune boosting" oversimplify a peptide that can enhance, suppress, or redirect signaling depending on biological context.
Supported
Topically administered LL-37 has been evaluated in randomized human studies of hard-to-heal venous leg ulcers, providing direct human wound-healing evidence.
Does not establish
Evidence boundary: Evidence for topical chronic-wound use does not establish efficacy for systemic infection, generalized immune enhancement, or injectable use.
Sources: Treatment with LL-37 is safe and effective in enhancing healing of hard-to-heal venous leg ulcers: a randomized, placebo-controlled clinical trial; Evaluation of LL-37 in healing of hard-to-heal venous leg ulcers: a multicentric prospective randomized placebo-controlled clinical trial
Supported
Human clinical investigation has also extended to LL-37-containing topical treatment in diabetic foot ulcers.
Does not establish
Evidence boundary: A wound-specific topical study should not be generalized to unrelated dermatologic, infectious, neurologic, or systemic indications.
Sources: Efficacy of LL-37 cream in enhancing healing of diabetic foot ulcer
Supported
LL-37 participates in complex inflammatory and host-defense pathways, and pathology studies have linked LL-37 biology to disease-promoting inflammatory processes in some settings; therefore it should not be characterized as universally protective.
Does not establish
Evidence boundary: Association or mechanistic contribution in a disease model does not prove that exogenous therapeutic LL-37 causes that disease.
Sources: Human antimicrobial peptide LL-37 contributes to Alzheimer's disease progression
Supported
LL-37 earns a higher evidence grade than most experimental peptides in Batch 7 because human randomized topical-wound trials exist, but that evidence remains route- and indication-specific and does not validate systemic research-market uses.
Does not establish
Evidence boundary: Grade B applies to the overall exact-compound evidence base, not to every proposed route or indication.
Sources: Treatment with LL-37 is safe and effective in enhancing healing of hard-to-heal venous leg ulcers: a randomized, placebo-controlled clinical trial; Evaluation of LL-37 in healing of hard-to-heal venous leg ulcers: a multicentric prospective randomized placebo-controlled clinical trial; Efficacy of LL-37 cream in enhancing healing of diabetic foot ulcer
Safety & Evidence Limitations
Considerations reported in the sources cited on this page — not a complete list of every possible risk, and not medical advice.
Safety Consideration
Topical wound-trial data cannot be generalized to systemic or injectable use.Safety Consideration
LL-37 can form complexes with self-DNA or self-RNA and amplify innate immune signaling in psoriasis-related models.Safety Consideration
FDA identifies immunogenicity, peptide impurity, API-characterization, reproductive, and tissue-specific protumorigenic concerns for compounded LL-37.Safety Consideration
Local reactions increased at the highest concentration in an early topical dose-ranging study.Safety Consideration
Long-term systemic safety is unknown.Safety Consideration
Uncertain sequence, salt, purity, and active-ingredient characterization; sterility and endotoxin risk for any non-topical route; possible cytotoxicity or tissue injury from membrane-disruptive activity at antimicrobial concentrations; unknown cardiovascular, renal, hepatic, neurologic, and hematologic effects; unknown interaction with antibiotics, immunosuppressants, cancer therapy, and autoimmune disease treatment; unknown effects on pregnancy, fertility, fetal development, and lactation. Topical short-term tolerability does not establish injectable or systemic safety.
Research Areas Being Studied
Research areas discussed on this page reflect the Anti-inflammatory / gut / skin research category and the sources cited below.
Findings Reported in Studies
Educational summary only — reported in cited studies, not a claim of proven benefit.
Show findings from 8 human studies
- Efficacy of LL-37 cream in enhancing healing of diabetic foot ulcer (2023):
- Evaluation of LL-37 in healing of hard-to-heal venous leg ulcers: a multicentric prospective randomized placebo-controlled clinical trial (2021):
- Treatment with LL-37 is safe and effective in enhancing healing of hard-to-heal venous leg ulcers: a randomized, placebo-controlled clinical trial (2014):
- Cathelicidin antimicrobial peptide LL-37 in psoriasis enables keratinocyte reactivity against TLR9 ligands (2012):
- Self-RNA-antimicrobial peptide complexes activate human dendritic cells through TLR7 and TLR8 (2009):
- Plasmacytoid dendritic cells sense self-DNA coupled with antimicrobial peptide LL37 in psoriasis (2007):
- LL-37 and Self-RNA-Mediated Inflammatory Signaling ():
- LL-37 as a T-Cell Autoantigen in Psoriasis ():
Study Tables by Evidence Type
14 study records · 1 with a Study-at-a-Glance summary
- Human Studies & Clinical Data 8
- Animal / Cell / Preclinical Data 1
- Regulatory Documents & Official Trial Registries 3
Human Studies & Clinical Data(8)
Efficacy of LL-37 cream in enhancing healing of diabetic foot ulcer
2023PMID 37480520 · DOI 10.1007/s00403-023-02657-8
- Population / Model
- Patients with mildly infected diabetic foot ulcers
- Dose / Duration / Finding
The study reported a higher wound-healing rate but did not show reductions in measured inflammatory cytokines or aerobic bacterial counts.
- Study/Trial Dosing:
- Topical LL-37 cream as defined in the publication's study design.
- Duration:
- Clinical wound-treatment study
Safety note
Small/local study; not evidence for systemic use.
Evaluation of LL-37 in healing of hard-to-heal venous leg ulcers: a multicentric prospective randomized placebo-controlled clinical trial
2021PMID 34687253 · DOI 10.1111/wrr.12977
- Population / Model
- Adults with hard-to-heal venous leg ulcers
- Dose / Duration / Finding
The phase 2b trial evaluated complete closure and healing outcomes; signals appeared dependent on ulcer size and did not establish broad efficacy.
- Study/Trial Dosing:
- Topical LL-37 at 0.5 or 1.6 mg/mL in the trial design.
- Duration:
- 4 weeks of treatment with follow-up
Safety note
Topical trial data cannot be generalized to systemic administration.
Treatment with LL-37 is safe and effective in enhancing healing of hard-to-heal venous leg ulcers: a randomized, placebo-controlled clinical trial
2014PMID 25041740
- Population / Model
- 34 adults with hard-to-heal venous leg ulcers
- Dose / Duration / Finding
Lower topical concentrations were associated with improved wound-healing-rate measures versus placebo in this small trial.
- Study/Trial Dosing:
- Topical LL-37 at 0.5, 1.6, or 3.2 mg/mL, applied in the study setting.
- Duration:
- 4 weeks
Safety note
Local reactions were more frequent at the highest concentration; topical wound use does not establish safety for systemic or injectable routes.
Cathelicidin antimicrobial peptide LL-37 in psoriasis enables keratinocyte reactivity against TLR9 ligands
2012PMID 21850017
- Population / Model
- Human psoriatic skin and keratinocyte models
- Dose / Duration / Finding
The study linked elevated LL-37 and TLR9-related signaling in psoriasis.
Safety note
Supports caution about immune activation; not an administered-treatment study.
Self-RNA-antimicrobial peptide complexes activate human dendritic cells through TLR7 and TLR8
2009PMID 19703986
- Population / Model
- Human immune cells and psoriasis-associated material
- Dose / Duration / Finding
LL-37 complexes with self-RNA activated innate immune signaling, illustrating context-dependent pro-inflammatory activity.
Safety note
Mechanistic human-cell evidence, not clinical dosing evidence.
Plasmacytoid dendritic cells sense self-DNA coupled with antimicrobial peptide LL37 in psoriasis
2007PMID 17873860
- Population / Model
- Human psoriasis tissue and immune-cell experiments
- Dose / Duration / Finding
LL-37–self-DNA complexes activated plasmacytoid dendritic cells, supporting a role in psoriasis pathogenesis.
Safety note
Mechanistic disease research; not an administered-treatment trial.
LL-37 and Self-RNA-Mediated Inflammatory Signaling
PMID 29507358
- Population / Model
- Dose / Duration / Finding
LL-37 can form complexes with self-RNA that stimulate innate immune signaling, contributing to inflammatory and autoimmune biology rather than acting as a simple immune enhancer. This is a distinct source record from the dataset's existing self-DNA (PMID 17873860) and self-RNA/TLR7-8 (PMID 19703986) studies, which carry different PMIDs.
Show full finding
LL-37 as a T-Cell Autoantigen in Psoriasis
PMID 25470744
- Population / Model
- Dose / Duration / Finding
LL-37 is recognized as a T-cell autoantigen in psoriasis, implicating it in autoimmune pathophysiology and contradicting simplistic claims that more LL-37 is always beneficial. Distinct source record from the dataset's existing PMID 21850017 (keratinocyte/TLR9 reactivity) study.
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Animal / Cell / Preclinical Data(1)
Human antimicrobial peptide LL-37 contributes to Alzheimer's disease progression
2022PMID 36138130
- Population / Model
- Dose / Duration / Finding
This work demonstrates that LL-37 can participate in inflammatory/pathologic signaling in an Alzheimer's-disease model context, underscoring that LL-37 is immunologically active rather than a uniformly beneficial antimicrobial peptide. It does not establish clinical toxicity from therapeutic LL-37 use.
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Regulatory Documents & Official Trial Registries(3)
Efficacy of LL-37 cream for diabetic foot ulcers
2019NCT04098562
Study-at-a-Glance available
- Population / Model
- Patients with diabetic foot ulcers
- Dose / Duration / Finding
Official trial registry record associated with topical LL-37 wound research.
Key takeaway
In 25 people with diabetic foot ulcers, LL-37 cream increased healthy new tissue (granulation) in the wound more than placebo. The change in wound size was not statistically significant. The trial was small.
Study at a Glance
Study at a Glance
Plain-language summary of: Efficacy of LL-37 cream for diabetic foot ulcers
Does LL-37 cream help diabetic foot ulcers heal?
Evidence status
What was being studied?
Whether a cream containing LL-37, a human antimicrobial peptide that was found at low levels in these ulcers, helps these ulcers heal. The study measured wound area, the proportion of the wound covered by healthy granulation (new red tissue), two inflammation chemicals in wound fluid (IL-1 alpha and TNF alpha), and the number of aerobic bacteria growing from the wound. This is about a topical cream on diabetic foot ulcers, not LL-37 taken or injected in other ways.
Who participated?
25 adults with diabetic foot ulcers who were screened in outpatient clinics in Jakarta, Indonesia, between January 2020 and June 2021: 13 received LL-37 cream and 12 received placebo cream. Average age was about 52 to 53; most had diabetes for over 10 years and ulcers present for over 4 weeks. Most ulcers were uninfected (9 and 8) and the rest had mild infection (4 in each group). The registry planned 40 people.
How was the study done?
A randomized, double-blind, placebo-controlled trial (registered as Phase 2). Participants applied either LL-37 cream (0.5 mg/mL) or a placebo cream twice a week for 4 weeks along with standard wound care. Wounds were photographed and measured on days 7, 14, 21 and 28 with ImageJ software, and wound fluid and bacterial cultures were collected. This summary uses the open-access full text of the journal paper and the registry record; the registry posts no results.
Key results
The proportion of the wound covered by granulation tissue rose more with LL-37 than with placebo at every time point: by 0.41 versus 0.16 on day 7, 0.60 versus 0.27 on day 14, 0.64 versus 0.30 on day 21 and 0.64 versus 0.36 on day 28 (P=0.031, 0.009, 0.006 and 0.037). Wound area shrank somewhat more with LL-37 (by 2.35 cm2 versus 1.54 cm2 on day 28), but the differences were not statistically significant on any day. IL-1 alpha and TNF alpha rose in both groups without a significant difference, and bacterial counts did not differ significantly between the groups.
| Measure | Group | Timepoint | Reported value |
|---|---|---|---|
| Increase in granulation index from day 1 (higher means more healthy new tissue) | LL-37 cream (13) vs placebo (12) | Days 7, 14, 21, 28 | Day 7: 0.41 vs 0.16; day 14: 0.60 vs 0.27; day 21: 0.64 vs 0.30; day 28: 0.64 vs 0.36P=0.031, 0.009, 0.006 and 0.037 (independent t test). |
| Decrease in wound area from day 1, cm2 | LL-37 cream vs placebo | Day 28 | -2.35 vs -1.54Greater with LL-37 on days 14, 21 and 28, but the differences were not statistically significant on any day (P>0.05). |
| Baseline wound-fluid LL-37 level, ng/mg protein (median) | LL-37 group vs placebo group | Day 1 | 1.07 vs 1.11Similar and low in both groups. |
What does this mean?
Safety findings
The paper reports no side effect directly caused by applying LL-37 cream. One of 13 participants in the LL-37 group had mild irritant contact dermatitis attributed to heavy wound drainage; it resolved after the dressing was changed to a silicone foam dressing. The paper does not report deaths or serious adverse events by group, and the registry posts no results.
Important limitations
- The study was small: 25 people analysed instead of the 40 planned, because COVID-19 restrictions hindered recruitment.
- Wound area, the more direct measure of healing, did not differ significantly between groups; only the granulation index did.
- The IL-1 alpha level was higher in the LL-37 group at the start (median 38.86 versus 12.07 pg/mg), which the authors list as a limitation.
- The trial lasted 4 weeks and included mostly uninfected or mildly infected ulcers, so it says little about larger, deeper or more infected wounds.
- It tested one topical cream concentration in one country; it does not apply to LL-37 given other ways.
- The registry record has not been updated since September 2019 and shows a planned size and dates that do not match the published study.
Regulatory context
- Investigational use studied here
- LL-37 cream (0.5 mg/mL) was studied as an investigational topical treatment for diabetic foot ulcers.
A search of Drugs@FDA and DailyMed on 2026-10-09 found no application or label for LL-37. No approval is implied.
Where sources differ
- Number of participants and study dates: ClinicalTrials.gov reports 40 participants (estimated); October 2019 to January 2020; status unknown; Archives of Dermatological Research paper reports 25 participants analysed (13 LL-37, 12 placebo); January 2020 to June 2021. The registry plans 40 people over a short 2019 to 2020 window; the paper reports 25 people recruited over about 18 months. The registry record was last updated in September 2019, before the study started, and still shows estimated figures. The paper says recruitment was hindered by COVID-19 restrictions and lists the small sample as its main limitation.
Sources
- Trial record
- ClinicalTrials.gov NCT04098562 (record last updated 2019; status shown as unknown; no results posted) — ClinicalTrials.gov
- Primary results source
- Archives of Dermatological Research 2023, LL-37 cream for diabetic foot ulcers (open-access full text, PMC10514151) (the peer-reviewed publication that reports the results of this trial) — PubMedClinicalTrials.gov is the trial record but posts no results for this study, so the results come from this publication. The journal paper states this registry number. The registry record predates the study and was never updated with results.
- Sources reviewed
- Trial registry record only · Full text reviewed · Regulatory document.
Other sources for this study (1)
- Drugs@FDA (openFDA) and DailyMed lookups for LL-37, accessed 2026-10-09 — Regulator (FDA / EMA) · No Drugs@FDA application and no DailyMed label were found.Content reviewed for this summary
This summary is a plain-language reading aid written by MitoCore. It does not replace the original study, which remains the authoritative source. Research information only, not medical advice.
FDA summary of identified safety risks for compounded cathelicidin LL-37
2026- Population / Model
- Dose / Duration / Finding
FDA states that compounded cathelicidin LL-37 may pose immunogenicity and peptide-impurity/API-characterization risks and that safety information is insufficient for proposed routes.
Safety note
FDA also cites nonclinical reproductive and tissue-specific protumorigenic concerns; this is compounding-risk context, not a finding that every LL-37 preparation causes those outcomes.
FDA Pharmacy Compounding Advisory Committee Future Meeting Page
- Population / Model
- Dose / Duration / Finding
FDA has announced that cathelicidin LL-37 is intended for future Pharmacy Compounding Advisory Committee discussion. No meeting date, advisory vote, final listing decision, or favorable FDA action was identified as of the research cutoff (2026-07-30). A future advisory review is not approval and does not establish compounding eligibility.
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Review Articles / Secondary Sources(2)
The human cathelicidin LL-37: a pore-forming antibacterial peptide and host-cell modulator
2016PMID 26556394
- Population / Model
- Dose / Duration / Finding
Review summarizes antimicrobial membrane activity and diverse host-cell signaling effects.
Safety note
Secondary overview; does not establish safety or efficacy for unapproved systemic use.
Emerging roles of the host defense peptide LL-37 in human cancer and its potential therapeutic applications
2010PMID 20521250
- Population / Model
- Dose / Duration / Finding
Review describes context-dependent tumor-promoting and tumor-suppressive observations across models.
Safety note
Secondary source; cancer effects are tissue- and model-dependent.
Anecdotal Reported Patterns — Not Medical Advice
Anecdotal Reported Patterns — Not Medical Advice
Reported dosing patterns are included for educational context only. They are self-reported, unverified, not medical advice, and not instructions for human use. Community-submitted patterns are not yet available in this Phase 1 prototype; this section is a placeholder reserved for moderated, aggregated community data.
Lab Markers to Discuss With a Clinician
Educational topics only — not self-monitoring instructions.
FAQ
Disclaimer
Educational information only. This page summarizes published and official research and does not provide medical advice, a recommendation, or instructions for human use.
Educational use only. This content is provided for informational and research-summary purposes only. It is not medical advice, not a treatment recommendation, not a dosing guide, and not a substitute for care from a licensed medical professional. Nothing here is intended to diagnose, treat, cure, prevent, or mitigate disease. Reported dosing patterns, when shown elsewhere on the site, must be labeled either as Study / Trial Dosing or Anecdotal Reported Patterns — Not Medical Advice. Community reports are self-reported, unverified, and not scientific proof.
Community-reported experiences, once enabled, must be displayed only as moderated, anonymized, or aggregated data. They are anecdotal, self-reported, unverified, and should never be presented as proof of safety, efficacy, or expected results.
Content status: Published. Last updated 2026-07-30.
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