[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)-gamma by stimulated human peripheral blood mononuclear cells (PBMNCs). They also efficiently inhibited the production of O2- by both unstimulated and IFN-gamma-activated human monocytes. Mouse IL-10 (mIL-10) also significantly inhibited the production of NO by lipopolysaccharide (LPS) and IFN-gamma-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-gamma and LPS. We also examined the effects of IL-4 and transforming growth factor (TGF)-beta 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-beta 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-gamma, 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-beta to suppress monocyte/macrophage activation in vivo.
Nemoto
Y
Y
First Department of Internal Medicine, Faculty of Medicine, Kyushu University.
Otsuka
T
T
Niiro
H
H
Kuga
S
S
Tanaka
Y
Y
Nakashima
H
H
Niho
Y
Y
D000818:Animals; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D016753:Interleukin-10 / Q000494:pharmacology*; D008262:Macrophage Activation; D008264:Macrophages / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D009000:Monocytes / Q000378:metabolism / Q000502:physiology*; D009569:Nitric Oxide / Q000096:biosynthesis; D013481:Superoxides / Q000378:metabolism
D013481:Superoxides; D016753:Interleukin-10; D009569:Nitric Oxide; D007371:Interferon-gamma