Kinetics of intraocular cytokines in the suppression of experimental autoimmune uveoretinitis by type I IFN |
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Authors: | Okada AA; Keino H; Suzuki J; Sakai J; Usui M; Mizuguchi J |
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Institution: | Department of Ophthalmology, Tokyo Medical College Hospital, Japan. |
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Abstract: | 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.
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