The relative contributions of
interleukin-12 (IL-12) and
IL-23 to viral pathogenesis have not been extensively studied.
IL-12p40 mRNA rapidly increases after neurotropic
coronavirus infection.
Infection of mice defective in both
IL-12 and
IL-23 (p40(-/-)), in
IL-12 alone (p35(-/-)), and in
IL-23 alone (p19(-/-)) revealed that the symptoms of coronavirus-induced
encephalitis are regulated by
IL-12. IL-17-producing cells never exceeded background levels, supporting a redundant role of
IL-23 in pathogenesis. Viral control, tropism, and
demyelination were all similar in p35(-/-), p19(-/-), and wild-type mice. Reduced morbidity in infected
IL-12 deficient mice was also not associated with altered recruitment or composition of inflammatory cells. However,
gamma interferon (IFN-gamma) levels and virus-specific IFN-gamma-secreting CD4 and CD8 T cells were all reduced in the central nervous systems (CNS) of infected p35(-/-) mice. Transcription of the proinflammatory
cytokines IL-1beta and
IL-6, but not
tumor necrosis factor, were initially reduced in infected p35(-/-) mice but increased to wild-type levels during peak
inflammation. Furthermore, although
transforming growth factor beta mRNA was not affected,
IL-10 was increased in the CNS in the absence of
IL-12. These data suggest that
IL-12 does not contribute to
antiviral function within the CNS but enhances morbidity associated with
viral encephalitis by increasing the ratio of IFN-gamma to protective
IL-10.