CHANGES IN BODY-TEMPERATURE AND CIRCULATING LEVELS OF INTERLEUKIN-6 AFTER INTRAARTERIAL INJECTIONS OR INFUSIONS OF TUMOR-NECROSIS-FACTOR-ALPHA IN GUINEA-PIGS

Tumor necrosis factor alpha (TNF) is released systematically during th e early phase of endotoxin induced fever(1). To study the effects of t his cytokine in guinea pigs, 2 mu g TNF were intra-arterially injected as a bolus or slowly infused within 60 min. Both modes of administrat ion induced a biphasic elevation of the animals' abdominal temperature lasting 6h and stimulated the release of endogenous interleukin-6 (IL -6)-like activity. The second phase of the thermal response and the re lease of endogenous IL-6-like activity were significantly higher, when TNF was slowly infused into the animals' circulation, in spite of a t ransiently higher TNF-like activity after the bolus injection of TNF. Both TNF and IL-6 may therefore be regarded as candidates to trigger t he febrile response in guinea pigs.