Premium
A study of the pyrogenic actions of interleukin‐1α and interleukin‐1β: interactions with a steroidal and a non‐steroidal anti‐inflammatory agent
Author(s) -
Davidson J.,
Milton A.S.,
Rotondo D.
Publication year - 1990
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1990.tb15843.x
Subject(s) - cytokine , alpha (finance) , pharmacology , chemistry , beta (programming language) , interleukin , dexamethasone , endocrinology , medicine , surgery , construct validity , computer science , patient satisfaction , programming language
1 The pyrogenic effects of intravenously 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 (TRI 2 , 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 , TRI 2 = 0.69 ± 0.04, n = 4) was approximately 5 fold more potent than IL‐1α (2500 u kg −1 , TRI 2 = 0.73 ± 0.07, n = 4, all values are means ± s.e.means) in elevating body temperature. Δ T 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.