Efeitos do abatacept no infiltrado inflamatório, na colagênese e na fibroplasia, em modelo de úlcera traumática de mucosa jugal de ratos.

Abstract

Abatacept is a monoclonal antibody synthetized from the fusion of the extracellular domain of the CTLA4 molecule with a modified fragment of human immunoglobulin G1 (IgG1) and is used in the treatment of rheumatoid arthritis and juvenile idiopathic arthritis. It is known for the regulation of T cell activation and modulation of inflammatory cytokines, and due to this to mechanisms it may interferes on wound healing. The aim of this study was to evaluate the ulcer’s healing process on buccal mucosa of males Wistar rats administered with Abatacept subcutaneously. The rats were randomized between a control group, injected with saline subcutaneously, and other three study groups, administered with Abatacept subcutaneously in the doses of 3.2 (ABA 3.2), 8 (ABA 8) and 20 mg/kg/week (ABA 20). The administration of saline and Abatacept was performed 14 days before oral ulcer induction and continued until euthanasia, performed on days 1, 3, 7, 14 and 21 after the ulcer induction. Oral ulcers of 8 mm diameter and 2 mm deep were induced on the left buccal mucosa. Histological slides were performed for histopathological (scores) and histomorphometric analysis, such as: polymorphonuclear, mononuclear, angiogenesis and fibroplasia. The collagenesis was evaluated by the Picrosirius Red staining. ANOVA-1-way and -2-way/Bonferroni and Kruskal-Wallis/Dunn were used in the statistical analysis (GraphPad Prism 5.0®, p<0.05). Abatacept administration decreased polymorphonuclear (p<0.001) and mononuclear count (p=0.027). However, there was an increase on the number of blood vessels (p<0,001) and the collagenesis (p<0.001) increased on days 3 and 7. In the ABA 20 group, the over Abatacept doses were related to late wound healing (p<0.001), reduced angiogenesis (p=0.017) and reduced fibroblasts (p<0,001). This study demonstrated that Abatacept accelerates ulcer healing on the buccal mucosa of male Wistar rats due to the reduced migration of inflammatory cells, meanwhile, higher doses were associated with delayed repair and extended expression of proinflammatory cytokines.