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

• Published in: American journal of physiology. Regulatory, integrative and comparative physiology Vol. 287; no. 4; p. R759
• Main Authors: Fortier, Marie-Eve, Kent, Stephen, Ashdown, Helen, Poole, Stephen, Boksa, Patricia, Luheshi, Giamal N
• Format: Journal Article
• Language: English
• Published: United States 01-10-2004
• Subjects: Animals; Antiviral Agents - pharmacology; Body Temperature - drug effects; Cyclooxygenase 2; DNA Primers; Eating - drug effects; Fever - chemically induced; Fever - physiopathology; Interleukin-1 - genetics; Interleukin-1 - physiology; Interleukin-6 - biosynthesis; Interleukin-6 - genetics; Isoenzymes - genetics; Isoenzymes - physiology; Lipopolysaccharides - pharmacology; Male; Poly I-C - pharmacology; Prostaglandin-Endoperoxide Synthases - genetics; Prostaglandin-Endoperoxide Synthases - physiology; Rats; Rats, Sprague-Dawley; Reverse Transcriptase Polymerase Chain Reaction; Tumor Necrosis Factor-alpha - biosynthesis; Tumor Necrosis Factor-alpha - genetics
• ISSN: 0363-6119
• DOI: 10.1152/ajpregu.00293.2004

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 degrees C above baseline was observed 3 h after an intraperitoneal injection of poly I:C (750 microg/kg). Pretreatment with IL-1ra diminished this response by >50% (maximum body temperature = 0.6 degrees 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)-alpha was also increased more than fourfold 2 h postinjection but remained unaffected by IL-1ra treatment. IL-1beta 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.