Pathogenic cytokines in thrombotic microangiopathies: molecular insights and therapeutic targets

Thrombotic microangiopathies (TMAs) are a heterogeneous group of disorders characterized by endothelial damage, microvascular thrombosis, thrombocytopenia, and microangiopathic hemolytic anemia. While the initiating triggers may differ-ranging from infections and autoimmune diseases to genetic complement dysregulation-a unifying pathophysiological feature is injury to the vascular endothelium. Recent advances have highlighted the critical role of pro-inflammatory cytokines in mediating endothelial dysfunction, contributing to both the initiation and propagation of thrombotic events in TMAs. Cytokines such as tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β) have been implicated in promoting endothelial activation, increased permeability, leukocyte adhesion, and procoagulant changes. These effects contribute to the loss of vascular integrity and the formation of microthrombi. Moreover, cytokine-mediated inflammation appears to be a common feature across various TMA subtypes, including Shiga toxin-associated hemolytic uremic syndrome (HUS), atypical HUS, thrombotic thrombocytopenic purpura (TTP), and secondary TMAs. The intensity and profile of cytokine involvement may vary, but their pathological influence on endothelial health remains a shared mechanism.