Sites of action of IL‐1 in the development of fever and cytokine responses to tissue inflammation in the rat

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Abstract
The objective of the present study was to determine the sites of action of the cytokine, interleukin‐1 (IL‐1), in the febrile response to local inflammation in the rat, by comparing the importance of IL‐1 in the local tissues, the circulation and the brain. This was achieved by injecting lipopolysaccharide (LPS, 100 μg kg−1) into a subcutaneous air pouch and testing the effects of blocking IL‐1 action with the human recombinant interleukin‐1 receptor antagonist (IL‐1ra) injected either into the air pouch, intraperitoneally (1 mg kg−1, 0+1 h, i.p.), or intracerebroventricularly (200 μg/rat, 0+1 h, i.c.v.). To investigate the effect of IL‐1ra on fever and the induction of local and circulating cytokines (IL‐1 and IL‐6), separate experiments were performed in which groups of animals were killed 1.5, 3 or 5 h after LPS injection. Plasma and pouch fluid samples were collected for bioassay of IL‐1 and IL‐6. Injection of LPS into the air pouch significantly increased (1.5°C) body temperature, local (air pouch) concentrations of bioactive IL‐1 and IL‐6, and circulating bioactive IL‐6, compared to saline‐treated controls. Injection of IL‐1ra into the pouch significantly attenuated LPS fever (PPBritish Journal of Pharmacology (1997) 120, 1274–1279; doi:10.1038/sj.bjp.0701049

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