LL-37: Safety Profile & Research Summary
24 Citacoes PubMedRevisado por EspecialistasCertificado GMPUltima Revisao: fevereiro de 2026
Resumo da Pesquisa Pre-clinica
Key Preclinical Studies
| Estudo | Modelo | Principais Achados | Ref |
|---|---|---|---|
| Zhang et al. (2022) | C57/BL6 mice, Pan02 PDAC — 20 mg/kg/day IP × 14d | 42% reduction in tumor growth (p<0.05); ↓ MDSCs and M2 macrofagos (p<0.01); ↑ CD4+/CD8+ T cells (p<0.01); fewer AEs vs gemcitabine | [11] |
| Overhage et al. (2008) | P. aeruginosa biofilm — 0.5 µg/mL | Inhibits biofilm formation via quorum-sensing downregulacao (Las/Rhl); promove twitching motility at sub-MIC | [7] |
| Wu et al. (2010) | Colon cancer cells | LL-37 inibe proteasome → ativa BMP signaling → p21Waf1 → cell cycle arrest | [10] |
| Koczulla et al. (2003) | Dexamethasone-treated mice — topico(a) LL-37 | Increased vascularization and re-epitelialization; key role in wound regeneration via angiogenese | [9] |
| Beaumont et al. (2014) | Bone marrow stromal cells | Stimulates proliferacao and osteogenic diferenciacao of BMSCs; recruits MSCs to injury sites | [14] |
| Tuberculosis (in vivo) | M. tuberculosis mice — ~1 mg/kg IT 3x/wk × 28d | 3–10 fold reduction in lung bacilli; eficaz against drug-sensitive and MDR strains | [7] |
Clinical Trials
| Ensaio | Population | Intervention | Key Results | Ref |
|---|---|---|---|---|
| Phase IIb VLU | n=148 | Topical 0.5 mg/mL, 3x/wk × 13 wk | Total population: NS. Subgroup (ulcers ≥10 cm²): 28.1% vs 8.1% closure (p=0.0458); healing rate 0.0367/day vs 0.0093/day (p=0.0439) | [16] |
| Phase I/II VLU | n=34 | Topical 0.5/1.6/3.2 mg/mL, 2x/wk × 4 wk | 0.5 mg/mL healing rate 6-fold higher do que placebo (p=0.003); ulcer area ↓ 68%; bell-shaped dose-response | [5] |
| RCT — DFU | n=25 | LL-37 cream 0.5 mg/g, 2x/wk × 4 wk | Granulation index significantly ↑ days 7–28 (p<0.05); 11/13 vs 3/12 alcancou >0.41 increase; no effect on bacterial load | [13] |
| Phase I Melanoma | n=36 planned | Intratumoral 250–2000 µg/tumor, weekly × 8 wk | Acceptable tolerability; variable biological response; dermatologic toxicity observado(a) | [17] |
Safety Summary
| Parametro | Finding |
|---|---|
| Clinical | Safe and bem tolerado(a) in 148-subject Phase IIb; no sistemico(a) safety concerns; mild local reactions (redness, edema) |
| Dose-Dependent | 3.2 mg/mL → aumentou local reactions; bell-shaped dose-response |
| Cytotoxicity | >13–25 µM towards eukaryotic cells; significantly inibido(a) por serum |
| Cancer Risk | Context-dependent: anti-tumorigenic in colon/gastric/pancreatic; pro-tumorigenic in breast/lung/ovarian/melanoma |
| Drug Interactions | Synergy with antibiotics (azithromycin, colistin, vancomycin); inibido(a) por glycosaminoglycans; Vitamin D upregula expression |
| Stability | Susceptible to protease degradacao; short plasma meia-vida; D-LL-37 enantiomer is protease-resistant |
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Aviso sobre Estudos In Vitro / Pré-clínicos: Os achados de pesquisa descritos acima foram observados em estudos laboratoriais (in vitro) e/ou em modelos animais. Esses resultados podem não se traduzir em desfechos humanos. Nenhuma alegação é feita em relação a aplicações terapêuticas humanas.
Apenas para Uso Educacional: Este conteúdo é fornecido apenas para fins informativos e educacionais. Não se destina a ser aconselhamento médico e não deve ser utilizado para diagnosticar, tratar, curar ou prevenir qualquer doença ou condição médica. Sempre consulte profissionais de saúde qualificados para decisões médicas.
Editorial Research Note
“Resumo da Pesquisa Pre-clinica Key Preclinical Studies EstudoModeloPrincipais AchadosRef Zhang et al.”
Referencias
- Johansson J, Gudmundsson GH, Rottenberg ME, et al. Conformation-dependent antibacterial activity do(a) naturally occurring human peptide LL-37. Journal of Biological Chemistry. 1998;273(6):3718-3724.
- Gudmundsson GH, Agerberth B, Odeberg J, et al. The human gene FALL39 and processing do(a) cathelin precursor para o(a) antibacterial peptide LL-37 in granulocytes. European Journal of Biochemistry. 1996;238(2):325-332.
- Ridyard KE, Overhage J. The Potential of Human Peptide LL-37 como um(a) Antimicrobial and Anti-Biofilm Agent. Antibiotics. 2021;10(6):650.
- Duplantier AJ, van Hoek ML. The Human Cathelicidin Antimicrobial Peptide LL-37 como um(a) Potential Treatment for Polymicrobial Infected Wounds. Frontiers in Immunology. 2013;4:143.
- Grönberg A, Mahlapuu M, Ståhle M, et al. 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;22(5):613-621.
- Yang B, Good D, Mosaiab T, et al. Significance of LL-37 on Immunomodulacao and Disease Outcome. BioMed Research International. 2020;2020:8349712.
- Heilborn JD, Nilsson MF, Kratz G, et al. The cathelicidin anti-microbial peptide LL-37 is envolveu in re-epitelialization of human skin wounds e e lacking in cronico(a) ulcer epithelium. Journal of Investigative Dermatology. 2003;120(3):379-389.
- Scott MG, Davidson DJ, Gold MR, et al. The human antimicrobial peptide LL-37 is a multifunctional modulator of innate resposta imunologicas. The Journal of Immunology. 2002;169(7):3883-3891.
- Svensson D, Nilsson BO. Human antimicrobial/host defense peptide LL-37 may prevent the spread of a local infection through multiplos(as) mechanisms: an update. Inflammation Research. 2025;74(1):36.
- Piktel E, Niemirowicz K, Wnorowska U, et al. The Role of Cathelicidin LL-37 in Cancer Development. Archivum Immunologiae et Therapiae Experimentalis. 2016;64(1):33-46.
- Zhang Z, Chen WQ, Zhang SQ, et al. The human cathelicidin peptide LL-37 inibe pancreatic cancer growth by suppressing autofagia and reprogramming do(a) tumor immune microenvironment. Frontiers in Pharmacology. 2022;13:906625.
- Lu F, Zhu Y, Zhang G, Liu Z. Renovation as innovation: Repurposing human antibacterial peptide LL-37 for cancer therapy. Frontiers in Pharmacology. 2022;13:944147.
- Miranda E, Bramono K, Yunir E, et al. Efficacy of LL-37 cream in enhancing healing of diabetic foot ulcer: a randomizado duplo-cego controlled trial. Archives of Dermatological Research. 2023;315(9):2623-2633.
- Seil M, Nagant C, Dehaye JP, et al. Spotlight on Human LL-37, an Immunomodulatory Peptide with Promising Cell-Penetrating Properties. Pharmaceuticals. 2010;3(11):3435-3460.
- Ergün FC, Kars MD, Kars G. Development and Characterization of LL37 Antimicrobial-Peptide-Loaded Chitosan Nanoparticles. Polymers. 2025;17(13):1884.
- Mahlapuu M, Sidorowicz A, Mikosinski J, et al. Evaluation of LL-37 in healing of hard-to-heal venous leg ulcers: A multicentric prospective randomizado controlado por placebo ensaio clinico. Wound Repair and Regeneration. 2021;29(6):938-950.
- Ohuchi K, Ikawa T, Amagai R, et al. LL-37 Might Promote Local Invasion of Melanoma by Activating Melanoma Cells and Tumor-Associated Macrophages. Cancers. 2023;15(6):1678.
- Miura S, Garcet S, Li X, et al. Cathelicidin Antimicrobial Peptide LL37 Induces Toll-Like Receptor 8 and Amplifies IL-36γ and IL-17C in Human Keratinocytes. Journal of Investigative Dermatology. 2023;143(5):832-841.e4.
- Lin X, Wang R, Mai S. Advances in delivery systems para o(a) therapeutic application of LL37. Journal of Drug Delivery Science and Technology. 2020;60(9):102016.
- Wu WK, Wang G, Coffelt SB, et al. Emerging Roles do(a) Host Defense Peptide LL-37 in Human Cancer e seu(sua) Potential Therapeutic Applications. International Journal of Cancer. 2010;127(8):1741-1747.
- Alalwani SM, Sierigk J, Herr C, et al. The antimicrobial peptide LL-37 modula the inflammatory and host defense response of human neutrofilos. European Journal of Immunology. 2010;40(4):1118-1126.
- Lozeau LD, Kole D, Dominko T, et al. Activity and toxicity of a recombinant LL37 antimicrobial peptide. Frontiers in Bioengineering and Biotechnology. 2016.
- Wan W, Zhang L, Lin Y, et al. Mitochondria-derived peptide MOTS-c: effects and mechanisms related to stress, metabolismo and aging. Journal of Translational Medicine. 2023;21(1):36.
- M.D. Anderson Cancer Center. Induction of Antitumor Response in Melanoma Patients Using the Antimicrobial Peptide LL37. ClinicalTrials.gov Protocol NCT02225366. 2015.
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