Abstract: | The effect of IFN-γ to stimulate formation of nitric oxide (NO) by normal murine peritoneal macrophages (M?) has been found to be completely dependent on the ability of IFN-γ to activate secretion of TNF-α. The NO-stimulatory effect of IFN-γ was abolished by anti-TNF-α antibodies, the inhibitory intervention of which could be fully reversed by exogenously supplied TNF-α. Accordingly, the failure of M? from C3H/HeJ mice to secrete TNF-α upon stimulation with IFN-γ was associated with their complete incapability to generate NO, unless they were simultaneously treated with IFN-γ + TNF-α. Collectively, the data document that similar to the NO up-regulatory action of other cytokines, the effect of IFN-γ is not independent, but depends on a synergistic cooperation with the self-produced TNF-α. The findings thus indicate that a widespread opinion claiming that IFN-γ per se is able to stimulate biosynthesis of NO needs revision. |