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Am J Physiol Regul Integr Comp Physiol 274: R741-R745, 1998;
0363-6119/98 $5.00
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Vol. 274, Issue 3, R741-R745, March 1998

TNF-alpha tolerance blocks LPS-induced hypophagia but LPS tolerance fails to prevent TNF-alpha -induced hypophagia

M. H. Porter, M. Arnold, and W. Langhans

Institute for Animal Sciences, Physiology and Animal Husbandry, Swiss Federal Institute of Technology, 8092 Zurich, Switzerland

To investigate the role of tumor necrosis factor-alpha (TNF-alpha ) in bacterial lipopolysaccharide (LPS)-induced hypophagia, we tested whether a cross tolerance between LPS and TNF-alpha exists with respect to their anorectic effects. Only the first of three subsequent intraperitoneal injections of LPS (100 µg/kg body wt) given every second day at dark onset (12:12-h light-dark cycle) led to a significant reduction of food intake in male rats. Likewise, intraperitoneal injections of human recombinant TNF-alpha (150 µg >=  3 × 106 U/kg body wt) also resulted in tolerance to its hypophagic effect. LPS tolerance did not alter the hypophagic response to subsequently injected TNF-alpha (n = 14). However, TNF-alpha pretreatment completely blocked the hypophagic response to LPS (n = 14). The results demonstrate that tolerance to the hypophagic effect of exogenous TNF-alpha is sufficient to eliminate LPS-induced hypophagia. This is consistent with the hypothesis that endogenous TNF-alpha plays a major role in LPS-induced hypophagia. The ineffectiveness of LPS tolerance to attenuate TNF-alpha -induced hypophagia is compatible with findings demonstrating that reduced TNF-alpha production is an important feature of LPS tolerance.

tumor necrosis factor-alpha ; lipopolysaccharide; anorexia; cytokine; endotoxin; food intake; feeding


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