Abstract
Purpose::
Experimental coronavirus retinopathy (ECOR) is an animal model of a progressive retinal degenerative disease. In susceptible mice (BALB/c) an acute retinal inflammation is followed by a chronic, immune-associated retinal degeneration and auto immune reactivity. In resistant mice (CD-1), acute retinal inflammation is followed by a complete recovery. In this study we evaluated cytokine profiles early in the course of this virus infection.
Methods::
BALB/c and CD-1 mice were inoculated with Mouse Hepatitis Virus (MHV), JHM strain or with PBS (mock injected) by the intravitreal route. Sera were evaluated from three groups of mice, virus injected, mock injected and untreated. Sera were collected in experiment 1 at 2, 4, 8 and 10 days post infection (PI) and in experiment 2 at days 1, 2, 3, and 4. Sera were analyzed by EIA for the presence of IFN-beta, IFN-gamma, IL-10 and IL-12.
Results::
Analysis of the cytokine profile during the first 4 days PI, revealed higher levels of IFN-beta, IFN-gamma, IL-10 and IL-12 in sera from BALB/c mice compared to levels observed in CD-1 mice. IFN-beta, IFN-gamma and IL-10 were not detected in sera from mock injected or untreated mice. At 2 and 3 days PI, 103 & 23 pg/ml of IFN-beta were observed in BALB/c mice compared to 5 & 30 pg/ml observed in CD-1 mice. Likewise, at 2 and 3 days PI, 444 & 243 pg/ml of IFN-gamma were observed in BALB/c mice compared to 26 & 25 pg/ml observed in CD-1 mice. In virus infected BABL/c mice IL-10 at concentrations of 10, 10, and 20 pg/ml was detected at day 2, 4 and 8 PI, respectively. In contrast, in virus infected CD-1 mice, IL-10 was detected only at day 2 PI at a concentration of 5 pg/ml. Low levels of IL-12 were detected in both strains of untreated mice and this was not altered by mock injection. At day 2 and 4 PI, the levels of IL-12 in sera from virus infected BABL/c mice were higher than those detected in CD-1 mice.
Conclusions::
These studies demonstrate that retinal degeneration in BALB/c mice is associated with an intense cytokine response early in the course of the infection. This highly augmented cytokine response is absent in the retinal degeneration resistant CD-1 mice. These studies indicate that a robust early cytokine response correlates with the development of retinal degeneration and retinal autoimmune reactivity.
Keywords: cytokines/chemokines • degenerations/dystrophies • inflammation