Related resources
Search for item elsewhere
University researcher(s)
Academic department(s)
Interleukin-1 receptor antagonist inhibits endotoxin fever and systemic interleukin-6 induction in the rat.
Luheshi G, Miller A, Brouwer S, Dascombe M, Rothwell NJ, Hopkins S
Am J Physiol. 1996;270( 1 Pt 1):E91-5.
Access to files
Full-text and supplementary files are not available from Manchester eScholar. Use our list of Related resources to find this item elsewhere. Alternatively, request a copy from the Library's Document supply service.
Abstract
Although a number of studies indicate that the pyrogenic activity of lipopolysaccharide (LPS) and/or interleukin (IL)-1 is mediated via induction of IL-6, this has been questioned by recent evidence demonstrating a dissociation between fever and circulating IL-6. The present study reexamines this relationship by use of human recombinant interleukin-1 receptor antagonist (IL-1ra). Injection of LPS (100 micrograms/kg ip) into rats induced fever (2.0 degrees C) that was significantly inhibited (P < 0.05) when IL-1ra (16 mg/kg ip) was given 1 and 2 h after LPS. The rise in plasma IL-6 preceded the febrile response by 1-1.5 h and, although the concentrations of bioactive IL-6 in plasma and cerebrospinal fluid (CSF) were not reduced at 4 h, at 2 h plasma and CSF IL-6 bioactivity was inhibited by 80 and 70%, respectively, after a single injection of IL-1ra (16 mg/kg ip). Intracerebroventricular injection of IL-1ra (200 micrograms/rat) inhibited LPS fever but did not affect the plasma IL-6 bioactivity measured 2 or 4 h after intraperitoneal LPS. These data show that peripheral IL-1 plays a part in the induction of both fever and the rise in plasma IL-6 that precedes it, and that IL-1 within the brain is also important in the induction of fever by LPS.
Keyword(s)
Animals; Injections, Intraperitoneal; Injections, Intraventricular; Male; Rats; Rats, Sprague-Dawley; Recombinant Proteins; Support, Non-U.S. Gov't; Time Factors; antagonists & inhibitors: Endotoxins; antagonists & inhibitors: Receptors, Interleukin-1; blood: Interleukin-1; blood: Interleukin-6; chemically induced: Fever; pharmacology: Lipopolysaccharides