Coronavirus infection of the retina is associated with increased levels of cytokines (IL-1, IL-6 and IFN-γ) within the vitreous

Purpose: The murine coronavirus (MHV) induces a biphasic retinal disease in BALB/c mice. This virus model allows us to explore virologie, immunologic and genetic aspects involved in the pathogenesis of retinal tissue damage. In this report, we evaluate the induction of cytokines within the vitreous. Methods. BALB/c mice were inoculated by the intravitreal route with 10^4.5 TCID₅₀ of virus or media. At varying times after inoculation, sera and eyes were removed. Formalin fixed samples were evaluated histologically and vitreous and serum samples were assayed for the presence of cytokines (IL-1α, IL-4, IL-6, TNF-α and IFN-γ) by ELISA assays. Frozen sections were immunocytochemically evaluated for lymphoid cells and virus. Results: Days 1-6 are associated with an acute retinal infection characterized by an infiltration of macrophages and T cells. At this time, elevated levels of IL-1α, IL-6 and IFN-γ were detected in the vitreous from virus infected mice in comparison to levels detected in mock injected or untreated mice. IL-6 was in 41% of vitreous samples from 27 virus infected mice whereas IL-6 was in 4% of 27 mock injected mice. IL-1α was in 50% of the vitreous samples from virus infected mice and was not detected in mock injected mice. Elevated cytokine levels in the vitreous did not correspond with serum levels. IL-4 and TNF-α were detected in all animals tested and did not correlate with infection. Days 10-21 are associated with the second phase of the infection, retinal degeneration. At this time, cytokine levels in the vitreous of virus infected mice were not different from levels detected in normal mice. Conclusion: These studies show that inflammatory cytokines, IL-1α, IL-6 and IFN-γ, are present within the vitreous during the early phase of the coronavirus - induced retinopathy. These data suggest that these cytokines may contribute to pathologic processes triggered by the virus infection.