LL-37

Research Reagent · Laboratory Use Only

What are the research findings on LL-37 peptide and its biological functions?

LL-37 is a human cathelicidin antimicrobial peptide (hCAP18/LL-37) with documented roles in innate immunity, wound healing, and anti-biofilm activity. Research published in PubMed indicates it disrupts bacterial membranes, modulates inflammation, and promotes angiogenesis. Preclinical studies also explore its potential in oncology and autoimmune conditions. It is not approved as a therapeutic agent.

Scientific AbstractPMID 42016145 · 2026

Objective

To investigate whether the immune response to LL-37 would be common among different ASCVD phenotypes.

Methods

Peripheral blood mononuclear cells (PBMCs) and plasma were collected from stable ASCVD patients enrolled within 12 months after MI or stroke or diagnosed with PAD. A subgroup of post-acute patients provided PBMCs at follow-up (14.7 ± 3.6 months). T-cell response to LL-37 was profiled using activation-induced markers. LL-37 IgG, immune complex (IC) levels and subclass were evaluated with ELISA. LDL is a reported binding partner of LL-37 in plasma. Therefore, cross-reactivity of LL-37 IgG-ICs with native LL-37 or LL-37 complexed with LDL (LL-37_LDL) was assessed using immune depletion.

Results

LL-37 provokes increased CD4+CD25+CD134+ T-cell response in stable post-MI patients whereas CD8+CD25+CD69+ T cells were reduced in PAD. CD4+ T-cell response to LL-37 in post-MI patients persisted at follow-up with increased CD4+CD25+CD69+FoxP3+ T regulatory cells while post-stroke patients had increased CD8+CD134+ T cells. LL-37 IgG-ICs were significantly increased in ASCVD patients with IgG3 subclass reduced in post-MI compared to post-stroke. Immune-depletion showed cross-reactivity of LL-37 IgG-ICs with both native LDL and LL-37_LDL only in post-MI plasma.

Conclusion

LL-37 antigen specific profiling of immune response may differentiate various ASCVD phenotypes and provide mechanistic insight in pathophysiology.

Mechanistic Research SummaryCurated from PubMed

This data is for laboratory research purposes only. Not for human or animal consumption.

What is LL-37?

LL-37 (cathelicidin antimicrobial peptide) is an endogenous antimicrobial peptide identified as an autoantigen in atherosclerotic cardiovascular disease (ASCVD). This research demonstrates that immune responses to LL-37 differ significantly across distinct ASCVD phenotypes (myocardial infarction, stroke, and peripheral artery disease).

Mechanism of Action

LL-37 functions as both a pathogen-defense molecule and an immunogenic epitope within atherosclerotic plaques. The peptide can form complexes with low-density lipoprotein (LDL) in plasma, creating a modified antigen that triggers differential T-cell and humoral immune responses. In post-MI patients, LL-37 stimulates CD4+ T-cell activation (marked by CD25 and CD134 expression) and promotes T regulatory cell (Foxp3+) differentiation, suggesting a shift toward adaptive immune control. Cross-reactivity between LL-37 immune complexes (IgG-ICs) and the LL-37_LDL complex indicates that lipid-peptide binding modulates immune recognition.

Observed Laboratory Results

  • Post-MI phenotype: Elevated CD4+CD25+CD134+ T-cell response persisted at 14.7-month follow-up with increased CD4+CD25+CD69+FoxP3+ regulatory T cells, indicating sustained CD4+ engagement and immune tolerance mechanisms.
  • PAD phenotype: Reduced CD8+CD25+CD69+ cytotoxic T-cell response, contrasting with the CD4-dominant post-MI profile and suggesting distinct immune surveillance pathways in peripheral vascular disease.
  • IgG subclass differentiation: IgG3 levels were significantly reduced in post-MI versus post-stroke patients, with LL-37 IgG-IC cross-reactivity to native LDL and LL-37_LDL detected exclusively in post-MI plasma, indicating phenotype-specific humoral immune targeting.
Clinical Research Parameters
10 trials

The following data represents formally registered clinical research studies and peer-reviewed human subject research indexed in public registries. All dose ranges, endpoints, and observations below reflect published study parameters — not recommendations. For research reference only.

ClinicalTrials.gov ↗
NCT02178488
COMPLETEDPhase IIn=60

Efficacy Study of Vitamin D Supplementation to Meticillin Resistant Staphylococcus Aureus (MRSA) Carriers

The purpose of this study is to treat persistent MRSA carriers with vitamin D supplementation during a 12 month to see if the number of MRSA positive patients can be reduced.

Study Interventions
Cholecalciferol, Placebo
Primary Endpoints
MRSA
Study Period
2014-12 → 2017-12
NCT02806414
COMPLETEDPhase I / Phase IIn=25

Evaluation of the Inhibitory Effects of Topical Ivermectin on Markers of Rosacea Specific Inflammation.

This study will assess the role of topical Ivermectin 1% cream and its effect on protease and antimicrobial peptide expression and on the skin microbiome (the microorganisms that live on the skin) in rosacea. This is a single-site 16-week open-label study at University of California, San Diego. The investigators will do this by first measuring serine protease activity and cathelicidin and skin mic

Study Interventions
Ivermectin
Primary Endpoints
Relative Trypsin-like Enzyme Activity
Study Period
2016-07 → 2021-05
NCT02138591
WITHDRAWNPhase III0

Therapeutic Benefit of Preoperative Supplemental Vitamin D in Patients Undergoing Major Surgical Procedures.

Vitamin D (Vitamin D) deficiency is very common. We recently showed that 97% of 204 patients admitted to Truman Medical Center were Vitamin D deficient (\<30 ng/ml). However, the consequences of Vitamin D deficiency, particularly with respect to infection, are not well understood. It is known that production of cathelicidin, an important antimicrobial peptide, is critically dependent upon Vitamin

Study Interventions
Blood draw pre-operatively, Blood draw post-operative Day 1, Blood draw post-operative Day 2
Primary Endpoints
Change in Vitamin D level as measured as 25-OHD level
Study Period
2016-02 → 2016-05
NCT01758081
ACTIVE NOT RECRUITINGN/An=25,874

Effects of Vitamin D and Omega-3 Fatty Acids on Infectious Diseases and hCAP18 (VITAL Infection)

The VITamin D and OmegA-3 TriaL (VITAL; NCT 01169259) is an ongoing randomized clinical trial in 25,875 U.S. men and women investigating whether taking daily dietary supplements of vitamin D3 (2000 IU) or omega-3 fatty acids (Omacor® fish oil, 1 gram) reduces the risk of developing cancer, heart disease, and stroke in people who do not have a prior history of these illnesses. This ancillary study

Study Interventions
vitamin D3, omega-3 fatty acids (fish oil), Vitamin D3 placebo
Primary Endpoints
upper respiratory infection; hCAP-18
Study Period
2010-07 → 2026-12
NCT01372995
COMPLETEDPhase IIn=31

Vitamin D in Ventilated ICU Patients

The increasing rate of hospital-acquired infection and antibiotic resistance are major causes of prolonged ICU stay and death in hospitalized patients. The enormous impact of ICU-related infection demands the need for cost-effective therapies that can be rapidly implemented to improve patient immune response to control infection. Unfortunately, little high-quality comparative effectiveness researc

Study Interventions
Enteral Vitamin D3 50,000 IU, Enteral Vitamin D3 100,000IU, Inactive substance
Primary Endpoints
Number of Participants With Plasma 25(OH)D Concentration >30ng/mL at Baseline; Number of Participants With Plasma 25(OH)D Concentration >30ng/mL at Day 7
Study Period
2011-07 → 2014-04
NCT05244018
COMPLETEDPhase IVn=80

Outcome of High Dose Vitamin D on Prognosis of Sepsis Requiring Mechanical Ventilation

There is a high prevalence of vitamin D deficiency in the critically ill patient population, with approximately 60% of patients found to be vitamin D deficient, (25(OH)D concentrations \<20 ng/mL) and an additional 30% of patients being vitamin D insufficient, (25(OH)D = 20-30 ng/mL).Approximately 80% of sepsis/septic shock patients experience respiratory failure and require mechanical ventilation

Study Interventions
Vitamin D3 tablets, Vitamin D tablets
Primary Endpoints
Change in procalcitonin level (ng/ml) and antimicrobial peptide cathelicidin (LL37) (ng/ml) level at day 7.
Study Period
2022-03-01 → 2022-10-31
NCT01398280
COMPLETEDEarly Phase In=15

Effects of Aminocaproic Acid (ACA) on Rosacea-specific Inflammation

The purpose of this study is to determine the effect of topical aminocaproic acid on the immune system by assessing the levels of antimicrobial peptides in the skin of patients with rosacea. It is hypothesized that aminocaproic acid applied topically will alter the body's immune system in patients with rosacea by inhibiting activation of antimicrobial peptides.

Study Interventions
Topical aminocaproic acid (ACA) mixed with Vanicream, Vehicle cream
Primary Endpoints
Kallikrein 5 (KLK5) Protease Activity
Study Period
2011-07 → 2012-12
NCT06867250
COMPLETEDN/An=33

Peri-implant Vitamin D and Cathelicidin (LL-37) Levels

This research aims to explore the influence of vitamin D on the body's defense system by examining its impact on specific proteins involved in immune response and inflammation in the soft tissues surrounding dental implants. Also aims to determine how vitamin D levels affect these proteins and their role in protecting peri-implant tissues from microbial infections and inflammation.

Study Interventions
The patients' periodontal clinical parameters were recorded. PISF samples were collected, and the evaluations of 25(OH)D and LL-37 were conducted using enzyme-linked immunosorbent assay.
Primary Endpoints
Peri-implant sulcus fluid vitamin D levels and clinical parameters correlation; The correlation between vitamin D and the antimicrobial peptide LL-37
Study Period
2021-04-01 → 2021-12-01
NCT04858217
RECRUITINGN/An=270

Periprosthetic Joint Infections: Diagnostic Accuracy and Cost-effectiveness Analysis of Serum and Synovial Markers

Total joint replacement (TJR) is an increasing effective procedure in orthopedics. However, TJR failure due to aseptic or septic loosening remains an important problem, often due to predisposing factors of the patient, which determine the need to perform a revision surgery. In light of the recent conclusions emerged on the still open problems concerning the diagnostic accuracy of serum and synovia

Primary Endpoints
White blood cell count (WBC, cells/μL); Erythrocyte sedimentation rate (ESR, mm/hour)
Study Period
2022-02-01 → 2026-03-31
NCT01580007
COMPLETEDPhase IIn=288

Clinical Trial of Phenylbutyrate and Vitamin D in Tuberculosis (TB)

Vitamin D exerts its effects via the Vitamin D Receptor (VDR) present in activated macrophages and induces expression and release of the cathelicidin, LL-37, a human antimicrobial peptide involved in killing of MTB. We aimed to investigate whether treatment of newly diagnosed pulmonary TB patients for 2 months with adjunctive PBA and vitamin D (Cholecalciferol) in combination with standard DOTS th

Study Interventions
Active Sodium Phenylbutyrate and active cholecalciferol, Placebo Sodium Phenylbutyrate plus active cholecalciferol, Active Sodium Phenylbutyrate and placebo cholecalciferol
Primary Endpoints
Proportion of pulmonary TB patients who are culture negative in sputum in week 4; Difference in improvement in clinical endpoints consisting of cough clearance, percentage chest x-ray clearance, fever remission and weight increase upto 8 weeks.
Study Period
2010-12 → 2014-12

All data presented on this page is for laboratory research purposes only. LL-37 is referenced here as a research reagent. This page does not constitute medical advice, clinical guidance, or endorsement of any compound for human or animal use. All referenced studies are available via PubMed (PMID: 42016145) and the DOI-linked journal publication. Researchers must consult applicable institutional and regulatory frameworks before conducting any protocols.