CYTOKINES PRODUCED EARLY IN PICORNAVIRUS INFECTION REFLECT RESISTANCEOR SUSCEPTIBILITY TO DISEASE

Gender bias favoring female resistance to picornavirus disease is not seen in ICR Swiss mice following infection with the MM strain of encep halomyocarditis virus (EMCV) (causing encephalitis and death) as it is with D variant of EMCV (causing diabetes in males), To define this di fference, an in vitro virus-infected splenocyte culture system was use d to explore virus effects on lymphoid cells. Infected and sham-infect ed splenocyte cultures, prepared from both genders of mice and infecte d with either virus variant, were examined for immunoregulatory cytoki nes in the first 24 h of infection using ELISA or bioassays, Disease r esistance was associated with increased levels of interferon-gamma (IF N-gamma) and undetectable levels of interleukin-10 (IL-10) by 12 h pos tinfection in splenocytes from ICR Swiss females infected with EMCV-D, Disease susceptibility was associated with high levels of IL-10 at 12 h after infection of spleen cells from ICR Swiss males infected with EMCV-D or from both genders infected with EMCV-MM, This information wa s used to protect susceptible mice against picornavirus disease (eithe r diabetes or death) by giving them an inducer of IFN-alpha/beta, to i nduce natural killer (NK)-like cells to produce high levels of IFN-gam ma and rat monoclonal anti-IL-10 to neutralize the effects of mouse IL -10.