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Am J Physiol Regul Integr Comp Physiol 278: R157-R165, 2000;
0363-6119/00 $5.00
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Vol. 278, Issue 1, R157-R165, January 2000

Role of hypothermia induced by tumor necrosis factor on apoptosis and function of inflammatory neutrophils in mice

Toshiko Mizuno1, Yukiko Kannan1, Midori Tokunaga1, Mitsuaki Moriyama1, Yasuo Kiso2,5, Ken Kusakabe2, Jyoji Yamate3, Kenichi Kiyomiya4, and Tsukasa Sugano1

1 Department of Veterinary Physiology, 2 Department of Veterinary Anatomy, 3 Department of Veterinary Pathology, and 4 Department of Toxicology, College of Agriculture, Osaka Prefecture University, Sakai 599-8531; and 5 Department of Veterinary Anatomy, Faculty of Agriculture, Yamaguchi University, Yamaguchi 753-8515, Japan

Changes in body temperature and cell infiltration, mediated by cytokines including tumor necrosis factor-alpha (TNF-alpha ), occur during inflammation, but a role of body temperature on inflammatory responses remains obscure. Intraperitoneal injection of 10% casein to mice resulted in transient hypothermia followed by neutrophil accumulation in peritoneal cavities. Peritoneal TNF-alpha was rapidly raised, and pretreatment of mice with an anti-TNF-alpha antibody promoted temperature restoration and partially inhibited neutrophil accumulation. To investigate direct effects of body temperature on neutrophils, peritoneal or peripheral blood neutrophils were cultured at 35°C or 37°C with or without recombinant murine TNF-alpha (100 ng/ml) or a protein synthesis inhibitor cycloheximide (1 µg/ml). Significant inhibition of spontaneous and TNF-alpha -induced apoptosis was obtained at 35°C compared with 37°C, an effect that was not altered by the addition of cycloheximide. Moreover, phagocytic ability of peritoneal neutrophils was significantly enhanced by incubating them at the lower temperature. These results indicate that mild hypothermia induced by endogenous TNF-alpha has enhancing roles on neutrophil survival and function during peritoneal inflammation.

inflammation; body temperature; tumor necrosis factor-alpha


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