A study of the pyrogenic actions of interleukin-1 alpha and interleukin-1 beta: interactions with a steroidal and a non-steroidal anti-inflammatory agent.
1. The pyrogenic effects of intravenously administered human recombinant interleukin-1 alpha (IL-1 alpha) and IL-1 beta were studied in the rabbit. 2. Both cytokines produced dose-related increases in body temperature. At all doses studied (100-5000 u kg-1) both cytokines elicited a monophasic increase in body temperature, beginning 15 min and reaching a maximum 45 min after administration. 3. A comparison of thermal response index (TRI2, the magnitude of febrile responses over 2 h obtained by integrating the change in temperature in degrees C against time in hours) values indicated that IL-1 beta (500 u kg-1, TRI2 = 0.69 +/- 0.04, n = 4) was approximately 5 fold more potent than IL-1 alpha (2500 u kg-1, TRI2 = 0.73 +/- 0.07, n = 4, all values are means +/- s.e.means) in elevating body temperature. delta Tmax values for the above doses of IL-1 beta and IL-1 alpha were 0.60 +/- 0.06 and 0.61 +/- 0.03 respectively. When IL-1 alpha and IL-1 beta were heated for 30 min at 60 degrees C prior to administration no biological activity was observed. 4. A cyclo-oxygenase inhibitor, ketoprofen (3 mg kg-1) administered 15 min before either cytokine completely abolished the fever induced by both IL-1 alpha (2500 u kg-1) and IL-1 beta (500 u kg-1). 5. Intravenous administration of the steroidal anti-inflammatory agent dexamethasone (3 mg kg-1) 1 h before either cytokine attenuated the fever induced by IL-1 alpha (2500 u kg-1) and IL-1 beta (500 u kg-1). 6. The effects of ketoprofen and dexamethasone on IL-I pyrogenicity indicate that prostanoids are almost certainly involved in the responses. The different potencies of IL-l alpha and IL-1 beta may be related to their relative ability to stimulate prostanoid biosynthesis.
Davidson
J
J
Department of Pharmacology, Marischal College, University of Aberdeen.
Milton
A S
AS
Rotondo
D
D
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001831:Body Temperature / Q000187:drug effects; D003907:Dexamethasone / Q000494:pharmacology; D004347:Drug Interactions; D007375:Interleukin-1 / Q000494:pharmacology*; D007660:Ketoprofen / Q000494:pharmacology; D008297:Male; D011749:Pyrogens; D011817:Rabbits; D011994:Recombinant Proteins / Q000494:pharmacology
D000893:Anti-Inflammatory Agents; D000894:Anti-Inflammatory Agents, Non-Steroidal; D007375:Interleukin-1; D011749:Pyrogens; D011994:Recombinant Proteins; D003907:Dexamethasone; D007660:Ketoprofen