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Am J Physiol Regul Integr Comp Physiol (June 29, 2006). doi:10.1152/ajpregu.00250.2006
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Submitted on April 11, 2006
Accepted on June 24, 2006

Oxy-resveratrol dampens neuroimmune responses in vivo: A selective effect on TNF{alpha}

A. Mouihate1*, Thomas F. Horn2, and Quentin J. Pittman3

1 Dept. of Physiology and Biophysics, University of Calgary, Calgary, Canada
2 Medical Neurobiology, University Magdeburg, Magdeburg, Germany
3 Dept. of Physiology & Biophysics, University of Calgary, Calgary, Canada

* To whom correspondence should be addressed. E-mail: mouihate{at}ucalgary.ca.

Consumption of nutrients rich in hydroxystilbenes has been promoted due to 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, TNF{alpha}, 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{alpha} production. In contrast to in vitro experiments, o-RES has no direct effect on NF-{kappa}B signaling pathway in vivo. The specific inhibitory effect of o-RES on TNF{alpha} opens new avenues for the clinical use of o-RES in pathological conditions where excessive production of TNF is deleterious.




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