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 suppress inflammation in rats with experimental autoimmune uveoretinitis (EAU); however, an effect on the systemic immune response was not identified. In order to investigate an immunological basis for suppression at the intraocular level, rats immunized with interphotoreceptor retinoid-binding protein (IRBP) were administered daily intramuscular injections of 10(5) IU IFN-alpha/beta and cytokines were measured by ELISA in intraocular extracts prepared by ultrasonification at various timepoints throughout the course of EAU. In control EAU, intraocular concentrations of IFN-gamma were found to be non-detectable on day 8 before the onset of inflammation, significantly elevated on day 12 at peak inflammation (182+/-106 pg/ml), then non-detectable again on day 16 after inflammation had begun to subside. In contrast, intraocular IFN-gamma in IFN-alpha/beta-treated rats remained non-detectable or low at all timepoints. Measurement of intraocular IL-2 revealed no difference between the two groups of rats. Intraocular IL-4 concentrations were elevated 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, intraocular 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 on day 16 in control EAU rats, while remaining non-detectable or low in IFN-alpha/beta-treated rats. These results suggest that acute inflammation in IRBP-induced EAU in rats involves both IFN-gamma and IL-10 at the local intraocular level, and that systemic administration of IFN-alpha/beta inhibits EAU via a mechanism that involves suppression of both cytokines.
Okada
A A
AA
Department of Ophthalmology, Tokyo Medical College Hospital, Japan.
Keino
H
H
Suzuki
J
J
Sakai
J
J
Usui
M
M
Mizuguchi
J
J
D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology* / Q000378:metabolism; D006224:Cricetinae; D016207:Cytokines / Q000378:metabolism*; D005123:Eye / Q000276:immunology / Q000378:metabolism*; D005260:Female; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007370:Interferon Type I / Q000494:pharmacology*; D007700:Kinetics; D051379:Mice; D051381:Rats; D011917:Rats, Inbred Lew; D012173:Retinitis / Q000276:immunology* / Q000378:metabolism; D014605:Uveitis / Q000276:immunology* / Q000378:metabolism
D016207:Cytokines; D007166:Immunosuppressive Agents; D007370:Interferon Type I