Gender variations in early Theiler's virus induced demyelinating disease: differential susceptibility and effects of IL-4, IL-10 and combined IL-4 with IL-10.

Theiler's murine encephalomyelitis virus (TMEV) induced demyelinating disease, is an animal model of multiple sclerosis (MS). The viral-induced encephalitis is followed by an inflammatory and demyelinating disease. We quantitated the response of female and male mice during the transition from encephalitis to early demyelination. CNS neuropathology and antiviral antibody production were evaluated. Parallel studies were done with anti-inflammatory cytokines IL-4, IL-10 or a combination of IL-4 with IL-10. Results show female mice demonstrate an augmented susceptibility to the virus and a greater response to the cytokine therapies. Significant variation was noted during early demyelinating disease. The combination therapy of IL-4 with IL-10 produced striking decreases in antiviral antibody levels and virus-induced neuropathologic disease. Male mice are less susceptible to viral-induced disease and are less responsive to the cytokine treatments. Gender bias in TMEV-induced demyelinating disease appears to parallel the differences noted with other experimental immune diseases.