Abatacept treatment impairs the cell migration and wound healing of oral ulcers in rats: Role of interleukin (IL)-1β,-6 and-10 and CD8/CD30 cells Influence of abatacept treatment on oral wound healing: Experimental model on rats

The present study aimed to evaluate the healing process of ulcers in the jugal mucosa of Wistar rats treated with abatacept. The rats were randomly assigned to four groups: saline-treated control (0.3 mL/kg) abatacept-treated groups at dosages of 3.2, 8.0 and 20.0 mg/kg/week. After two weeks of subcutaneous (SC) administration, ulcers were introduced into the left jugal mucosa with an 8-mm diameter punch. SC administration was continued until euthanasia (after 1, 3, 7, 14 and 21 days of ulceration), and ulcers were clinically measured and animals weighed. Histological slides were evaluated (healing scores and polymorphonuclear, mononuclear, vessel, and fibroblast/myofibroblast counts). We also performed collagenesis analysis (Picrosirius Red) and immunohistochemistry (induced nitric oxide synthase (iNOS), interleukin (IL)-1beta (1 beta), -6, -10, plus the analysis of CD8 and CD30). The experiment was repeated to perform a vascular permeability assay. ANOVA 1-way or 2-way/Bonferroni and Kruskal-Wallis/Dunn tests were used for statistical analysis (GraphPad Prism 5.0 (R), p < 0.05). Abatacept treatment reduced the ulcer diameter and the numbers of polymorphonuclear and mononuclear cells; reduced the CD8+/CD30+ ratio and vascular permeability; and increased collagenesis and IL-10 expression at the beginning of the protocol. At the highest dose, there was a delay in repair and vascular proliferation; a reduction in the number of fibroblasts/myofibroblasts; and prolongation of iNOS, IL- and IL-expression. We conclude that abatacept accelerates the healing of oral ulcers by reducing the migration of inflammatory cells, but overdose of abatacept leads to delayed repair and prolongation of proinflammatory cytokine expression.