Abstract:Antibodies against hepatitis C virus (HCV) were detected in 18 (2.3 %)

We studied the potential role of a cytokine regulatory mechanism(s) in LPS-dependent reprogramming and modulation of TNF-α and nitric oxide (NO) responses in mouse peritoneal macrophages. Reciprocal regulation of TNF-α and NO production by LPS-primed and LPS-stimulated macrophages was found to be dependent on the presence of soluble secretory products released by the cells during the initial LPS priming interaction. Pretreatment of naïve macrophages with different mouse recombinant cytokines such as rIL-10, rIL-12, and rIFN-γ dose dependently and differentially regulated subsequent LPS-induced production of TNF-α, IL-6, and NO by cytokine-primed cells. Analysis of IL-12 and IL-10 levels present in culture supernatants of LPS-primed and LPS-stimulated macrophages revealed a high degree of correlation between the profiles of TNF-α and IL-12 as well as NO and IL-10. Furthermore, LPS priming of macrophages in the presence of anti-IL-12-neutralizing mAb attenuated TNF-α responses while at the same time up-regulated NO production. In contrast, neutralization of endogenous IL-10 with anti-IL-10 mAb resulted in considerable TNF-α response at LPS priming doses under conditions that would otherwise strongly inhibit TNF-α production. We also found that the initial LPS priming of naïve macrophages differentially and dose dependently regulates expression of mRNAs for IL-10, IL-12, and IFN-γ in LPS-primed macrophages. Collectively, our data provide experimental support for the hypothesis that a cytokine regulatory network, most probably autocrine, tightly controls the reciprocal modulation of TNF-α and NO responses in LPS-primed macrophages.

No abstract