Effect of type I interferon on experimental autoimmune uveoretinitis in rats

In order to establish a scientific basis for the potential use of type I interferons (IFNs) in clinical uveitis, we examined the effect of a preparation of IFN-alpha/beta on experimental autoimmune uveoretinitis (EAU). Lewis rats were immunized with bovine interphotoreceptor retinoid-binding protein (IRBP) and given daily intramuscular injections of 10(5) IU mouse natural IFN-alpha/beta. Intraocular inflammation was assessed by slit-lamp biomicroscopy and histopathological examination. Rats treated daily with IFN-alpha/beta starting on the day of IRBP immunization showed decreased intraocular inflammation as well as a slight delay in onset of inflammation when compared to control rats. This effect was also observed to a lesser extent in rats treated during either the induction phase of EAU only, or starting immediately after the onset of inflammation in the effector phase of EAU. Measurement of IRBP-stimulated splenocyte proliferation and serum anti-IRBP antibody subtypes did not reveal a significant difference between IFN-alpha/beta-treated rats and control rats. Measurement of cytokine production by IRBP-stimulated splenocytes in vitro showed significantly decreased TNF-alpha for IFN-alpha/beta-treated rats compared to control, but no difference for IFN-gamma, IL-2, IL-4, and IL-10. These results indicate that systemic administration of IFN-alpha/beta suppresses IRBP-induced EAU in rats, and suggest that such suppression may be mediated in part by a reduction in TNF-alpha production.