Experimental autoimmune uveitis (EAU) is mediated by CD4+ T cells. The immunopathogenic process results from the effects of proinflammatory cytokines elaborated by the uveitogenic T cells. Inhibition of the activities of these cytokines is a therapeutic goal in the treatment of inflammatory ocular diseases. Suppressors of cytokine signaling (SOCS) are a family of endogenous feed-back regulators of cytokine activities. In this study, we examined the potential involvement of SOCS in recovery from EAU by analyzing the kinetics of SOCS expression during the course of the disease in Lewis rats. Lewis rats were immunized with S-Antigen (S-Ag) or IRBP in complete Freund's adjuvant. At various time points during the course of the disease, eyes were removed for pathology and retinal RNA isolation. All animals were extensively perfused before enucleation and retinal preparation to minimize contamination with blood cells. SOCS mRNA expression was analyzed by RT-PCR. We found constitutive expression of low levels of CIS and SOCS3 transcripts in the eye. However, the levels of these transcripts, as well as those of SOCS1 and SOCS2 increased dramatically at onset of disease. This high leve of SOCS expression was sustained for 48-72 hrs after which a rapid decline was observed for all of the SOCS except CIS. Similar results were observed in S-Ag or IRBP immunized rats but not in unimmunized or rats that received only CFA. Constitutive expression of SOCS transcripts in the retina suggests that SOCS proteins may function in vivo as a fail-safe mechanism to negatively regulate the activities of proinflammatory cytokines in the vertebrate retina. Enhanced expression of SOCS genes at the onset of EAU and sustained expression of CIS through out the course of EAU suggest that SOCS proteins may complement the protective effects of Th2 cytokines such as IL-10, IL-4 or TGF-b in EAU. Constitutive and inducible expression of these negative regulators of cytokine signaling make them particularly attractive neuroprotective agents.
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