The viral mimic, polyinosinic:polycytidylic acid, induces fever in rats via an interleukin-1-dependent mechanism.
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.
Fortier
Marie-Eve
ME
Douglas Hospital Research Centre, McGill Univ., 6875 LaSalle Boulevard, Verdun, Quebec, Canada.
Kent
Stephen
S
Ashdown
Helen
H
Poole
Stephen
S
Boksa
Patricia
P
Luheshi
Giamal N
GN
D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D001831:Body Temperature / Q000187:drug effects; D051546:Cyclooxygenase 2; D017931:DNA Primers; D004435:Eating / Q000187:drug effects; D005334:Fever / Q000139:chemically induced* / Q000503:physiopathology*; D007375:Interleukin-1 / Q000235:genetics / Q000502:physiology*; D015850:Interleukin-6 / Q000096:biosynthesis / Q000235:genetics; D007527:Isoenzymes / Q000235:genetics / Q000502:physiology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D011070:Poly I-C / Q000494:pharmacology*; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000235:genetics
D000998:Antiviral Agents; D017931:DNA Primers; D007375:Interleukin-1; D015850:Interleukin-6; D007527:Isoenzymes; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D011070:Poly I-C