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 tosuppress inflammation in rats with experimental autoimmune uveoretinitis(EAU); however, an effect on the systemic immune response was notidentified. In order to investigate an immunological basis for suppressionat the intraocular level, rats immunized with interphotoreceptorretinoid-binding protein (IRBP) were administered daily intramuscularinjections of 10(5) IU IFN-alpha/beta and cytokines were measured by ELISAin intraocular extracts prepared by ultrasonification at various timepointsthroughout the course of EAU. In control EAU, intraocular concentrations ofIFN-gamma were found to be non-detectable on day 8 before the onset ofinflammation, significantly elevated on day 12 at peak inflammation(182+/-106 pg/ml), then non-detectable again on day 16 after inflammationhad begun to subside. In contrast, intraocular IFN-gamma in IFN-alpha/beta-treated rats remained non-detectable or low at all timepoints. Measurementof intraocular IL-2 revealed no difference between the two groups of rats.Intraocular IL-4 concentrations were elevated in rats treated withIFN-alpha/beta, although this cytokine was also detected in the same rangein controls as well as normal rats. Finally, intraocular IL-10 wasnon-detectable on day 8, significantly elevated at peak inflammation on day12 (588+/-139 pg/ml), then decreased to low levels on day 16 in control EAUrats, while remaining non-detectable or low in IFN-alpha/beta-treated rats.These results suggest that acute inflammation in IRBP-induced EAU in ratsinvolves both IFN-gamma and IL- 10 at the local intraocular level, and thatsystemic administration of IFN-alpha/beta inhibits EAU via a mechanism thatinvolves suppression of both cytokines.