IL-1β Antagonist Receptor Peptide Associated with Photobiomodulation Accelerates Diabetic Wound Tissue Repair

• Published in: Inflammation Vol. 47; no. 4; pp. 1262 - 1277
• Main Authors: Zaccaron, Rubya Pereira, de Roch Casagrande, Laura, Venturini, Ligia Milanez, Bittencourt, João Vitor Silvano, da Costa, Camila, de Pieri, Ellen, Thirupathi, Anand, Rezin, Gislaine Tezza, Machado-de-Ávila, Ricardo Andrez, Silveira, Paulo Cesar Lock
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.08.2024; Springer Nature B.V
• Subjects: Biomedical and Life Sciences; Biomedicine; Collagen (type III); Cytokines; Cytotoxicity; Diabetes; Diabetes mellitus; Gene expression; Hyperglycemia; IL-1β; Immunology; Inflammation; Internal Medicine; Pathology; Peptides; Pharmacology/Toxicology; Redox properties; Rheumatology; Skin diseases; Skin lesions; Streptozocin; Transforming growth factor-b; Wound healing; photobiomodulation; peptide; diabetic wound; inflammation; oxidative stress
• ISSN: 0360-3997; 1573-2576; 1573-2576
• DOI: 10.1007/s10753-024-01974-y

Chronic hyperglycemia caused by diabetes mellitus (DM) slows down the healing process due to prolonged inflammation which impedes the regeneration progression. Photobiomodulation (PBM) is considered a non-pharmacological intervention and has anti-inflammatory and biostimulatory effects that accelerate the healing process. Currently found IL-1β inhibitors are difficult to implement due to their cytotoxic potential, excessive amounts, and invasive administration, and therefore, the application of this peptide in diabetic wounds represents a promising intervention to help resolve the inflammatory response. This study aimed to investigate the effect of an IL-1β inhibitor molecule associated with PBM irradiation in a model of epithelial injury in diabetic mice. After the induction of the DM model with streptozotocin (STZ), the skin lesion model was implemented through surgical excision. Sixty C57BL/6 mice divided into five experimental groups ( n  = 12) were used: excisional wound (EW), DM + EW, DM + EW + DAP 1–2 (inhibitor peptide), DM + EW + PBM, and DM + EW + PBM + DAP 1–2. Treatment started 12 h after wound induction and was performed daily for 5 days. Twenty-four hours after the last application, the animals were euthanized and the outer edge of the wound was removed. The results obtained demonstrate that the DM + EW + PBM + DAP 1–2 group caused a reduction in the levels of pro-inflammatory cytokines, an increase in anti-inflammatory cytokines, and an increase in TGF-β and maintenance of the cellular redox state with a consequent reduction in levels of inflammatory infiltrate and concomitant stimulation of type III collagen gene expression, as well as a decrease in the size of the wound in square centimeter 6 days after the injury. Only the combination of therapies was able to favor the process of tissue regeneration due to the development of an approach capable of acting at different stages of the regenerative process, through the mechanisms of action of interventions on the inflammatory process by avoiding its stagnation and stimulating progression of regeneration.