Elevated expression of IL-12 and IL-23 in patients with primary immune thrombocytopenia

Abstract

Immune thrombocytopenia (ITP) is an acquired autoimmune disorder. Both impaired platelet production and T-cell-mediated effects play a role in ITP. A T-helper1 (Th1) polarization of the immune response and up-regulation of Th17 cells have been demonstrated in ITP patients. Interleukin (IL)-12 and IL-23 produced by antigen presenting cells are essential for inducing and sustaining Th1 and Th17 effector cells via different pathways. However, less is known with regard to the levels of expression and synthesis of these two cytokines in patients with ITP. This was determined in this study in 46 patients with ITP as well as in 22 healthy controls. Our results showed that an increased expression of IL-12 p40, IL-12 p35, and IL-23 p19 mRNA was observed in bone marrow mononuclear cells and peripheral blood mononuclear cells of patients with ITP compared with controls. Consequently, higher levels of IL-12 and IL-23 were also found in bone marrow plasma and peripheral blood plasma in patients with ITP than in controls. Afterwards, a markedly higher level of IL-12 and IL-23 in bone marrow plasma or peripheral blood plasma was found in patients with chronic ITP than in patients with acute ITP. Furthermore, the peripheral blood plasma levels of IL-12 and IL-23 were negative correlated with platelet counts in ITP patients. Therefore, the augmented expression of IL-12 and IL-23 in patients with ITP may play an important role in the pathogenesis of this disease.

Decreased levels of immune-regulatory cytokines in patients with immune thrombocytopenia and long-lasting overexpression of these cytokines in the splenectomized patients

“…Interestingly, among the members of the IL‐12 family (which consists of IL‐12, IL‐23, IL‐27, and IL‐35), IL‐12 and IL‐23 are proinflammatory cytokines with important effects on Th1 and Th17 commitment, whereas IL‐27 and IL‐35 mainly exert immune regulatory functions 29 . Previous studies demonstrated that ITP patients had high levels of IL‐12 and IL‐23, whereas we here report lower serum IL‐27 and IL‐35 levels in newly diagnosed ITP patients, indicating that the imbalance of IL‐12 family member cytokines might be a cytokine profile signature in ITP patients 30 …”

“…29 Previous studies demonstrated that ITP patients had high levels of IL-12 and IL-23, whereas we here report lower serum IL-27 and IL-35 levels in newly diagnosed ITP patients, indicating that the imbalance of IL-12 family member cytokines might be a cytokine profile signature in ITP patients. 30…”

Immune Response in Severe and Non-Severe Coronavirus Disease 2019 (COVID-19) Infection: A Mechanistic Landscape

“…Severe samples were also enriched for genes associated with an increased response to IL-12, a proinflammatory cytokine. JAK-STAT activation and subsequent IFN-γ generation, after IL-12 stimulation, have been previously reported in patients with immune thrombocytopenia ( 59 ).…”

Biology of interleukin‑37 and its role in autoimmune diseases (Review)

“…Serum IL-37 levels and IL-18Rα + /CD4 + T-cell ratios are negatively correlated with PLT counts ( 102 ). IL-37 expression is significantly higher in patients with active ITP, and can regulate the expression of several cytokines to exert anti-inflammatory effects ( 103 ). In terms of the possible mechanisms involving IL-37 in the pathogenesis of ITP, it is speculated that IL-37 may promote Th2 cell function by influencing cytokine expression and inhibiting the immune response effects of Th1 and Th17, thereby alleviating the inflammatory responses.…”