Kinetics of intraocular cytokines in the suppression of experimental autoimmune uveoretinitis by type I IFN

The systemic administration of IFN-alpha/beta was previously found to suppr ess inflammation in rats with experimental autoimmune uveoretinitis (EAU); however, an effect on the systemic immune response was not identified, In o rder to investigate an immunological basis for suppression at the intraocul ar level, rats immunized with interphotoreceptor retinoid-binding protein ( IRBP) were administered daily intramuscular injections of 10(5) IU IFN-alph a/beta and cytokines were measured by ELISA in intraocular extracts prepare d by ultrasonification at various timepoints throughout the course of EAU, In control EAU, intraocular concentrations of IFN-gamma were found to be na n-detectable on day 8 before the onset of inflammation, significantly eleva ted an day 12 at peak inflammation (182 +/- 106 pg/ml), then non-detectable again on day 16 after inflammation had begun to subside, In contrast, intr aocular IFN-gamma in IFN-alpha/beta-treated rats remained non-detectable or low at all timepoints, Measurement of intraocular IL-2 revealed no differe nce between the two groups of rats. Intraocular IL-4 concentrations were el evated in rats treated with IFN-alpha/beta, although this cytokine was also detected in the same range in controls as well as normal rats, Finally, in traocular IL-10 was non-detectable on day 8, significantly elevated at peak inflammation on day 12 (588 +/- 139 pg/ml), then decreased to low levels o n day 16 in control EAU rats, while remaining nondetectable or low in IFN-a lpha/beta-treated rats, These results suggest that acute inflammation in IR BP-induced EAU in rats involves both IFN-gamma and IL-10 at the local intra ocular level, and that systemic administration of IFN-alpha/beta inhibits E AU via a mechanism that involves suppression of both cytokines.