title: Oxyresveratrol dampens neuroimmune responses in vivo: a selective effect on TNF-alpha.
abstract: 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)-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-kappaB 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-alpha is deleterious.
authors.affiliation: Hotchkiss Brain Institute, Dept. of Physiology and Biophysics, Faculty of Medicine, Univ. of Calgary, 3330 Hospital Dr., NW, Calgary, Alberta T2N 4N1, Canada. mouihate@ucalgary.ca
authors.forename: A
authors.initials: A
authors.lastname: Mouihate
authors.forename: T F
authors.initials: TF
authors.lastname: Horn
authors.forename: Q J
authors.initials: QJ
authors.lastname: Pittman
mesh_terms: D000818:Animals; D051546:Cyclooxygenase 2 / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D005334:Fever / Q000209:etiology / Q000503:physiopathology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D007031:Hypothalamus / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000009:adverse effects / Q000494:pharmacology; D008297:Male; D016328:NF-kappa B / Q000502:physiology; D015213:Neuroimmunomodulation / Q000187:drug effects* / Q000502:physiology*; D011301:Preoptic Area / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000502:physiology; D013267:Stilbenes / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000187:drug effects / Q000378:metabolism*
chemical_list: D015850:Interleukin-6; D008070:Lipopolysaccharides; D016328:NF-kappa B; D013267:Stilbenes; D014409:Tumor Necrosis Factor-alpha; C515052:trans-2,3',4,5'-tetrahydroxystilbene; D051546:Cyclooxygenase 2; C489691:Ptgs2 protein, rat