Cascade of fever production in mice infected with influenza virus.
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)-1 alpha, an endogenous pyrogen, rose markedly in serum among cytokines (IL-1 alpha, IL-2, IFN-gamma, and tumor necrosis factor-alpha) examined. Fever was induced 14 hr after intraperitoneal IFN-alpha treatment and IL-1 alpha level rose significantly in the serum of the IFN-alpha-treated mice as compared with that of untreated mice. Fever production was significantly suppressed by treatment with anti-IFN-alpha/beta or anti-IL-1 alpha antibody in infected mice and the former significantly suppressed responsive IL-1 alpha production, indicating that elevated IFN activity induced IL-1 alpha production and subsequently fever production in infected mice. The activity of cyclooxygenase (COX) that produces prostaglandin (PG)E2 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-1 alpha level was maintained at the elevated level. Therefore, influenza infection in mice turned on the following cascade for fever induction: IFN production, IL-1 alpha production, elevated COX activity, and PGE2 production. We elucidated the relationship among IFN activity, IL-1 alpha production and COX activity and demonstrated the cascade of fever production in influenza infection.
Kurokawa
M
M
Department of Virology, Toyama Medical and Pharmaceutical University, Japan.
Imakita
M
M
Kumeda
C A
CA
Shiraki
K
K
D000818:Animals; D000906:Antibodies / Q000276:immunology; D002460:Cell Line; D016207:Cytokines / Q000096:biosynthesis; D004195:Disease Models, Animal; D005260:Female; D005334:Fever / Q000276:immunology*; D006801:Humans; D009980:Influenza A virus / Q000276:immunology*; D007251:Influenza, Human / Q000276:immunology*; D016898:Interferon-alpha / Q000276:immunology / Q000494:pharmacology; D007375:Interleukin-1 / Q000276:immunology; D051379:Mice; D008815:Mice, Inbred Strains; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism
D000906:Antibodies; D016207:Cytokines; D016898:Interferon-alpha; D007375:Interleukin-1; D011451:Prostaglandin-Endoperoxide Synthases