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INFLAMMATION AND CYTOKINES

The viral mimic, polyinosinic:polycytidylic acid, induces fever in rats via an interleukin-1-dependent mechanism

¹Department of Psychiatry, McGill University, Douglas Hospital Research Centre, Montreal, Quebec, Canada H4H 1R3; ²School of Psychological Science, La Trobe University, Bundoora, Victoria 3086, Australia; and ³National Institute for Biological Standards and Control, Potters Bar, United Kingdom EN6 3QG

Submitted 4 May 2004 ; accepted in final form 14 June 2004

Polyinosinic:polycytidylic acid (poly I:C) is a synthetic double-stranded RNA that is used experimentally to model viral infections in vivo. Previous studies investigating the inflammatory properties of this agent in rodents demonstrated that it is a potent pyrogen. However, the mechanisms underlying this response have not been fully elucidated. In the current study, we examined the effects of peripheral administration of poly I:C on body temperature and cytokine production. Male rats were implanted with biotelemetry devices and randomly assigned to one of the following three groups: poly I:C + saline, poly I:C + interleukin-1 receptor antagonist (IL-1ra), or saline + saline. Maximal fever of 1.6°C above baseline was observed 3 h after an intraperitoneal injection of poly I:C (750 µg/kg). Pretreatment with IL-1ra diminished this response by >50% (maximum body temperature = 0.6°C above baseline). Plasma IL-6 concentration increased fivefold 2 h post-poly I:C compared with saline-injected rats; levels returned to baseline 4 h postinjection. Pretreatment with IL-1ra prevented this rise in IL-6. Plasma tumor necrosis factor (TNF)- was also increased more than fourfold 2 h postinjection but remained unaffected by IL-1ra treatment. IL-1 and cyclooxygenase-2 mRNA were significantly upregulated in the hypothalamus of poly I:C-treated animals. Finally, poly I:C decreased food intake by 30%, but this response was not altered by pretreatment with IL-1ra. These results suggest that poly I:C induces fever, but not anorexia, through an IL-1 and prostaglandin-dependent mechanism.

cytokines; fever; food intake

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