Tumor Necrosis Factor-α Blockade Corrects Monocyte/Macrophage Imbalance in Primary Immune Thrombocytopenia

Primary immune thrombocytopenia (ITP) is an acquired autoimmune bleeding disorder. Monocytes and macrophages are the major cells involved in autoantibody-mediated platelet clearance in ITP. In the present study, we found increased percentages of peripheral blood proinflammatory CD16(+) monocytes and elevated frequencies of splenic tumor necrosis factor-alpha (TNF-alpha)-expressing macrophages in ITP patients compared with healthy controls. Concurrently, we observed elevated TNF-alpha secretion in plasma as well as higher TNF-alpha mRNA expression in total peripheral blood mononuclear cells and CD14(+) monocytes of ITP patients. Of note, in vitro TNF-alpha blockade with neutralizing antibody remarkably reduced polarization to M1 macrophages by inhibiting the nuclear factor kappa B (NF-kappa B) signaling pathway. Moreover, TNF-alpha blockade dampened macrophage phagocytosis and T cell stimulatory capacity. Finally, in passive and active murine models of ITP, anti-TNF-alpha therapy reduced the number of nonclassical monocytes and M1 macrophages, ameliorated the retention of platelets in spleen and liver, and increased the platelet count of ITP mice. Taken together, TNF-alpha blockade decreased the number and function of proinflammatory subsets of monocytes and macrophages by inhibiting the NF-kappa B signaling pathway, leading to remarkable attenuation of antibody-mediated platelet destruction. Thus, TNF-alpha blockade may be a promising therapeutic strategy for the management of ITP.

Automated summary

The study found increased proinflammatory CD16(+) monocytes in peripheral blood of ITP patients and elevated TNF-alpha-expressing macrophages in the spleen. TNF-alpha blockade reduced the number and function of proinflammatory subsets of monocytes and macrophages, leading to remarkable attenuation of antibody-mediated platelet destruction.