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Cascade of fever production in mice infected with influenza virus
Author(s) -
Kurokawa Masahiko,
Imakita Masami,
Kumeda Cristina A.,
Shiraki Kimiyasu
Publication year - 1996
Publication title -
journal of medical virology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.782
H-Index - 121
eISSN - 1096-9071
pISSN - 0146-6615
DOI - 10.1002/(sici)1096-9071(199610)50:2<152::aid-jmv8>3.0.co;2-9
Subject(s) - virus , alpha (finance) , virology , tumor necrosis factor alpha , immunology , alpha interferon , biology , orthomyxoviridae , interferon , influenza a virus , medicine , construct validity , nursing , patient satisfaction
The cascade of fever production in influenza was studied. To analyse fever production in a murine model, we selected DBA/2 mice that have the highest susceptibility in fibrile responses among seven mouse strains. Intranasal influenza infection‐ and interferon (IFN)‐induced fever production was studied in this mouse model. Fever was induced prominently on day 2 after influenza infection and IFN activity was also increased in serum. Only the level of interleukin (IL)‐1α, an endogenous pyrogen, rose markedly in serum among cytokines (IL‐1α, IL‐2, IFN‐γ, and tumor necrosis factor‐α) examined. Fever was induced 14 hr after intraperitoneal IFN‐α treatment and IL‐1α level rose significantly in the serum of the IFN‐α‐treated mice as compared with that of untreated mice. Fever production was significantly suppressed by treatment with anti‐IFN‐α/β or anti‐IL‐1α antibody in infected mice and the former signficantly suppressed responsive IL‐1α production, indicating that elevated IFN activity induced IL‐1α production and subsequently fever production in infected mice. The activity of cyclooxygenase (COX) that produces prostaglandin (PG)E 2 was significantly augmented in the brain of infected mice on day 2 after infection. Fever production was suppressed by the inhibition of COX activity with aspirin, although IL‐1α level was maintained at the elevated level. Therefore, influenza infection in mice turned on the following cascade for fever induction: IFN production, IL‐1α production, elevated COX activity, and PGE 2 production. We elucidated the relationship among IFN activity, IL‐1α production and COX activity and demonstrated the cascade of fever production in influenza infection. © 1996 Wiley‐Liss, Inc.