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Physiology and Pharmacology of Temperature Regulation

Oxyresveratrol dampens neuroimmune responses in vivo: a selective effect on TNF-

¹Hotchkiss Brain Institute, Department of Physiology and Biophysics, University of Calgary, Calgary, Alberta, Canada; and ²Institute for Medical Neurobiology, Otto-von-Guericke University Magdeburg, Magdeburg, Germany

Submitted 11 April 2006 ; accepted in final form 24 June 2006

Consumption of nutrients rich in hydroxystilbenes has been promoted because of their health benefits, including dampening of inflammatory responses. However, few studies have examined their effects in vivo. Here, we show that the hydroxystilbene oxyresveratrol (trans-2,3',4,5'-tetrahydroxystilbene: o-RES) blocked hypothermia but caused no significant effect on the febrile response to the immune stimulus, bacterial LPS in rats. This was associated with a reduction in the LPS-induced plasma cytokine, tumor necrosis factor (TNF)-, but not IL-6. Both IL-6-stimulated STAT-3 and LPS-induced cycoloxygenase-2 expression in the hypothalamus were not affected by o-RES. These data strongly suggest that the o-RES-induced dampening of neuroimmune responses is largely due to its inhibitory effect on TNF- production. In contrast to in vitro experiments, o-RES has no direct effect on NF-B signaling pathway in vivo. The specific inhibitory effect of o-RES on TNF- opens new avenues for the clinical use of o-RES in pathological conditions where excessive production of TNF- is deleterious.

hypothalamus; liver; nuclear factor-B; STAT-3; cyclooxygenase-2

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