Abstract
We investigated the protective role of chloroquine against pristane-induced macrophage activation, oxidative stress, and Th1/Th2 skewness in C57BL/6J mice. Those mice were treated with pristane alone or combined with chloroquine. Hematological and biochemical parameters, macrophage phagocytic function, the oxidant/antioxidant index, cytokine for IFN-γ, TNF-α, IL-4, and IL-6, and the isotypes of IgG2a and IgG1 were determined. And the expression of T-bet/GATA-3 and IL-12/IL-10 mRNA in spleen were analyzed by real-time PCR. We found that pristane treatment for a period of 12 or 24 weeks triggered macrophage activation syndrome, characterized by hemophagocytosis in spleen and peripheral blood, enhanced lipid phagocytosis by peritoneal macrophages in vitro, erythropenia and leucopenia, increased anti-Smith, lactic dehydrogenase, triglyceride, and ferritin, as well as hypercytokinemia of IFN-γ, TNF-α, IL-4, and IL-6. In parallel, a significant increase in lipid peroxidation and a decrease in superoxide dismutase, glutathione, and catalase activity, as well as a skewed Th1/Th2 balance in spleen, were observed. However, chloroquine supplementation showed a remarkable amelioration of these abnormalities. Our data indicate that pristane administration induces macrophage activation, oxidative stress, and Th1/Th2 skewness, which can be attenuated by chloroquine.
Highlights
The hemophagocytic syndrome, termed macrophage activation syndrome (MAS) in the context of autoimmune diseases, is a life-threatening disease of severe hyperinflammation
The present results firstly demonstrate that a single intraperitoneal injection of pristane triggered macrophage activation syndrome, characterized by hemophagocytosis in spleen and peripheral blood, enhanced lipid phagocytosis by peritoneal macrophages in vitro, erythropenia and leucopenia, and hypercytokinemia, as well as increased lactic dehydrogenase, triglyceride, and ferritin in serum
Emerging evidence suggests that CD4+T-helper cells can be divided into Th1 and Th2 subsets based upon the cytokines they produce, which are mutually antagonistic
Summary
The hemophagocytic syndrome, termed macrophage activation syndrome (MAS) in the context of autoimmune diseases, is a life-threatening disease of severe hyperinflammation. It is characterized by fever, splenomegaly, cytopenias affecting at least 2 of 3 lineages in the peripheral blood, hyperferritinemia, hypertriglyceridemia and/or hypofibrinogenemia, hemophagocytosis in the bone marrow, spleen, or lymph nodes, and so forth [1]. It is reported that a skew toward T-helper (Th) 1 immune response has been observed in MAS patients [2]. The Th1 cells upon activation secrete proinflammatory cytokines: interleukin- (IL-) 12, interferon- (IFN-) γ, and tumor necrosis factor- (TNF-) α, which mainly activate macrophages to produce reactive oxygen species (ROS) and mediate innate immunity [3]. Convincing data suggested oxidative stress and the Th1 cytokine levels correlated with systemic lupus erythematosus (SLE) disease activity [4]
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