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: Parul Kapil, Roscoe Atkinson, Chandran Ramakrishna, Daniel J Cua, Cornelia C Bergmann, Stephen A Stohlman
• Journal: Journal of virology (J Virol) Vol. 83 Issue 12 Pg. 5978-86 (Jun 2009) ISSN: 1098-5514 [Electronic] United States
• PMID: 19339350 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Interleukin-12 Subunit p40
• Interleukin-23
• Interleukin-10
• Interferon-gamma

Topics

• Animals
• Cells, Cultured
• Central Nervous System (immunology, virology)
• Coronavirus Infections (immunology)
• Demyelinating Diseases (immunology, virology)
• Encephalitis, Viral (immunology)
• Interferon-gamma (immunology)
• Interleukin-10 (immunology)
• Interleukin-12 Subunit p40 (deficiency, immunology)
• Interleukin-23 (deficiency, immunology)
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Murine hepatitis virus (immunology)