Anti-inflammatory profile of Ac2-26 peptide in experimental autoimmune uveitis

Introduction: Uveitis is associated with several autoimmune diseases, being one of the main causes of blindness in the world. In recent years, the role of the anti-inflammatory protein annexin A1 (AnxA1) in ocular inflammatory processes has been investigated in vivo and in vitro, and point to AnxA1 as one of the essential mediators in homeostasis of the inflammatory process. Objectives: to investigate, in vivo, in the experimental autoimmune uveitis (EAU), the effects of the Ac2-26, an AnxA1 mimetic peptide, administered in prevention and therapeutic protocols. Methods: Lewis rats were divided into induced-untreated (EAU), treated preventively (P) or therapeutically (T) and control (C) groups (n=10/group). For the development of the EAU, inoculation with bovine interphotoreceptor retinoid-binding protein (IRBP) (100 µg) in complete Freund's adjuvant emulsion (100 µl) occurred in the right paw of the animals. Simultaneously, an intraperitoneal (i.p.) injection containing Bordetella pertussis toxin (0.5 µg in 100 µl PBS) was administered as an additional adjuvant. Treated animals received Ac2-26 (200 µg in 200 µl of PBS) by i.p. daily from day 1 to day 13 post-immunization (P) and from day 8 to day 13 post-immunization (T). Animals without manipulation were used as a control group. EAU severity was assessed daily in all groups. The quantification of leukocytes was performed in aqueous humor (AqH), CD4+ and CD8+ lymphocytes. The cytokines interferon (IFN)-γ, tumor necrosis factor (TNF)-α, interleukin (IL)-2, IL-4, IL-10, IL-17 and monocyte chemoattractant protein (MCP)-1 were measured in the ocular macerate supernatant. Results: Clinically, the eyes of the EAU-induced rats showed altered macroscopic characteristics, and in the treated groups, normal parameters were reestablished. Leukocytes, predominantly lymphocytes, were found in the untreated-EAU group, while the quantification of CD4+, CD8+ showed a reduction of these cells in the treated animals. Furthermore, reduced levels of IL-2, IFN-γ and IL-10 occurred in the groups that received mimetic peptide treatment compared to untreated animals. Conclusion: Our results indicate that the administration of Ac2-26 promoted effective anti-inflammatory effects in this experimental autoimmune uveitis model, with potential for therapeutic application.