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1 Department o Psychiatry, McGill University, Douglas Hospital Research Centre, Montreal, Quebec, Canada
2 Department o Psychiatry, McGill University, Douglas Hospital Research Centre, Montreal, Quebec, Canada; School of Psychological Science, La Trobe University, Bundoora, Australia
3 National Institute for Biological Standards and Control, Potters Bar, United Kingdom
* To whom correspondence should be addressed. E-mail: giamal.luheshi{at}mcgill.ca.
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 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 3h after an intraperitoneal (i.p.) injection of poly I:C (750 µg/kg). Pre-treatment with IL-1ra diminished this response by more than 50% (maximum body temperature = 0.6 °C above baseline). Plasma IL-6 concentration increased 5-fold 2h post-poly I:C compared to saline injected rats; levels returned to baseline 4h post-injection. Pre-treatment with IL-1ra prevented this rise in IL-6. Plasma tumor necrosis factor (TNF)-
was also increased more than 4-fold 2h post-injection, 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 pre-treatment with IL-1ra. These results suggest that poly I:C induces fever, but not anorexia, through an IL-1 and prostaglandin dependent mechanism.
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