1. The pyrogenic effects of inravenously administered human recombinant interleukin-1α (IL-1α) and IL-1β 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 °C against time in hours) values indicated that IL-1β (500 u kg-1, TRI2 = 0.69 ± 0.04, n = 4) was approximately 5 fold more potent than IL-1α (2500 u kg-1, TRI2 = 0.73 ± 0.07, n = 4, all values are means ± s.e. means) in elevating body temperature. ΔT(max) values for the above doses of IL-1β and IL-1α were 0.60 ± 0.06 and 0.61 ± 0.03 respectively. When IL-1α and IL-1β were heated for 30 min at 60°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-1α (2500 u kg-1) and IL-1β (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-1α (2500 u kg-1) and IL-1β (500 u kg-1). 6. The effects of ketoprofen and dexamethasone on IL-1 pyrogenicity indicate that prostanoids are almost certainly involved in the responses. The different potencies of IL-1α and IL-1β may be related to their relative ability to stimulate prostanoid biosynthesis.
