title: Interleukin-12 (IL-12), but not IL-23, deficiency ameliorates viral encephalitis without affecting viral control.
abstract: 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.
authors.affiliation: Department of Neuroscience NC30, Lerner Research Institute, The Cleveland Clinic Foundation, Cleveland, OH 44195, USA.
authors.forename: Parul
authors.initials: P
authors.lastname: Kapil
authors.forename: Roscoe
authors.initials: R
authors.lastname: Atkinson
authors.forename: Chandran
authors.initials: C
authors.lastname: Ramakrishna
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Cua
authors.forename: Cornelia C
authors.initials: CC
authors.lastname: Bergmann
authors.forename: Stephen A
authors.initials: SA
authors.lastname: Stohlman