Inhibitory Effects of Interleukin (IL)-10 and Viral IL-10 (vIL-10) on the Functions of Monocytes/Macrophages

In this study, we examined the effects of IL-10 and vIL-10 on the production of superoxide anion (O₂ ^-) and nitric oxide (NO) by human monocytes and mouse macrophages. At an optimal concentration, human IL-10 (hIL-10) and vIL-10 significantly inhibited the production of interferon (IFN)-γ by stimulated human peripheral blood mononuclear cells (PBMNCs). They also efficiently inhibited the production of O₂ ^- by both unstimulated and IFN-γ-activated human monocytes. Mouse IL-10 (mIL-10) also significantly inhibited the production of NO by lipopolysaccharide (LPS) and IFN-γ-stimulated mouse peritoneal macrophages. Moreover, the production of O₂ ^- and NO was effectively suppressed whether the IL-10 was added before or together with the stimulus, indicating that this cytokine acts primarily at an early stage of monocyte/macrophage activation by IFN-γ and LPS. We also examined the effects of IL-4 and transforming growth factor (TGF)-β on the production of O₂ ^- and NO by human monocytes and mouse macrophages, and found that they significantly inhibited both the production of O₂ ^- by human monocytes and the production of NO by mouse macrophages. Moreover, a combination of any two of IL-10, IL-4 and TGF-β caused an additive effect on the inhibition of O₂ ^- production by human monocytes. These results indicated that IL-10 suppresses monocyte/macrophage activation either indirectly via an inhibition of the synthesis of IFN-γ, a potent monocyte/macrophage activator, by PBMNCs, or directly via the deactivation of monocytes/macrophages. Moreover IL-10 may act in concert with IL-4 and TGF-β to suppress monocyte/macrophage activation in vivo.