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

Abstract

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-α (TNF-α)-expressing macrophages in ITP patients compared with healthy controls. Concurrently, we observed elevated TNF-α secretion in plasma as well as higher TNF-α mRNA expression in total peripheral blood mononuclear cells and CD14+ monocytes of ITP patients. Of note, in vitro TNF-α blockade with neutralizing antibody remarkably reduced polarization to M1 macrophages by inhibiting the nuclear factor kappa B (NF-κB) signaling pathway. Moreover, TNF-α blockade dampened macrophage phagocytosis and T cell stimulatory capacity. Finally, in passive and active murine models of ITP, anti-TNF-α 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-α blockade decreased the number and function of proinflammatory subsets of monocytes and macrophages by inhibiting the NF-κB signaling pathway, leading to remarkable attenuation of antibody-mediated platelet destruction. Thus, TNF-α blockade may be a promising therapeutic strategy for the management of ITP.

Investigation of the Active Compounds and Important Pathways of Huaiqihuang Granule for the Treatment of Immune Thrombocytopenia Using Network Pharmacology and Molecular Docking

“…TNF-α blockade decreased antibody-mediated platelet destruction and may be a promising therapeutic strategy for the management of ITP [32]. Anti-TNF-α 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 [32].…”

“…Other active components, like adenosine, a purinergic signaling molecule, showed good binding affinities with EGFR, TNF, STAT3, and ERBB2 than prototype ligands and were a well-known actor of the immune system and the inflammatory response both in physiologic and pathologic conditions 50]. It hypothesized that HQHG blocks TNF-α signaling pathway, resulting in remarkable attenuation of antibody-mediated platelet destruction [32]. This study investigated the intricate mechanism of HQHG treatment for ITP by utilizing an integrated network pharmacological and pharmacokinetics strategy.…”

Evaluation of paediatric immune thrombocytopenia patients with clinical and laboratory findings: emphasizing the role of monocytosis

“…Disruption of T cell homeostasis is also thought to be one of the important reasons for the loss of immune tolerance in ITP. In clinical studies, it has been shown that CD16+ proinflammatory monocytes stimulate the Th1 response in the pathogenesis of ITP, and suppression of the proinflammatory monocyte response as a possible therapeutic target has been attempted to be targeted in vitro [47]. As a result, monocyte increase may be one of the main causes of immune dysregulation and may play different roles in the pathogenesis of ITP.…”

Membranous nephropathy complicated by immune thrombocytopenia treated with low-density lipoprotein apheresis: a case report and literature review

“…First, lipid absorption directly lowers the levels of inflammatory cytokines, such as tumor necrosis factor (TNF)-α [16], which are significantly elevated in patients with ITP [17]. Zhao et al reported that anti-TNF-α therapy reduced the number of non-classical monocytes and M1 macrophages and increased the platelet count in an ITP murine model [18]. Second, LDL-A suppresses the hyperactivation of macrophages [16,19], which are crucial for ITP pathogenesis by acting both as effector cells, phagocytizing platelets, and as antigen presenting cells, stimulating autoantibodies against platelet production [20].…”