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A second injection 48 h later caused a further diminution of IFN\u2010\u03b3 pc down to 30% of the number generated in splenocyte cultures of phosphate\u2010buffered saline (PBS)\u2010injected controls. Injection of Lewis rats with either one or two doses of HgCl<jats:sub>2<\/jats:sub> revealed no inhibitory effect on splenic IFN\u2010\u03b3 production.<\/jats:p><jats:p>The presence of the reduced form of glutathione (GSH) in the culture medium was found to be essential in these experiments. In the absence of GSH there was an overall 20\u2010fold reduction of the number of IFN\u2010\u03b3 pc in splenocyte cultures of normal or PBS\u2010injected rats, which was further reduced to a 60\u2010 to 70\u2010fold\u2010lower level in cultures of rats exposed to HgCl2. This mercury\u2010mediated extra reduction could be fully reversed with an excess (2 mM) of GSH in Lewis but not in BN splenocyte cultures. Since the bivalent Hg<jats:sup>2+<\/jats:sup> ion is known to bind to and inactivate sulfydryl groups of proteins and low molecular weight thiols, most notably GSH, we investigated a possible role for thiols in IFN\u2010\u03b3 production. It was found that the generation of IFN\u2010y pc in normal BN and Lewis splenocyte cultures was strongly dependent on GSH or its precursor cysteine in the culture medium. Other thiol compounds were also effective but disulfides were completely inactive. Depletion of intracellular GSH in ConA\u2010stimulated splenocytes by buthionine sulfoximide (BSO), an inhibitor of <jats:italic>de novo<\/jats:italic> GSH biosynthesis, strongly inhibited the generation of IFN\u2010\u03b3 pc. The inhibitory effect of BSO was not abolished by the addition of interleukin\u20102 (IL\u20102), but was mimicked with antibodies directed to the IL\u20102 receptor. The data stress the importance of GSH in the enhancement of IL\u20102\u2010mediated IFN\u2010\u03b3 production and are most consistent with a model in which mercury interferes with T cell IFN\u2010\u03b3 production by affecting the intracellular availability of GSH. The strain\u2010specific susceptibility to mercury\u2010mediated inhibition of IFN\u2010\u03b3 production is discussed.<\/jats:p>","DOI":"10.1002\/eji.1830230316","type":"journal-article","created":{"date-parts":[[2007,3,1]],"date-time":"2007-03-01T18:48:33Z","timestamp":1172774913000},"page":"675-681","source":"Crossref","is-referenced-by-count":41,"title":["Mercuric chloride down\u2010regulates T cell interferon\u2010\u03b3 Production in Brown Norway but not in Lewis rats; role of glutathione"],"prefix":"10.1002","volume":"23","author":[{"given":"Peter H.","family":"Van Der Meide","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Miranda C. D. 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