PS1480 INTERLEUKIN‐37 REDUCES INFLAMMATION AND IMPAIRS PHAGOCYTOSIS OF PLATELETS IN IMMUNE THROMBOCYTOPENIA

Abstract

Background:Immune thrombocytopenia (ITP) is an autoimmune and inflammatory disease characterized by low platelet count with heterogeneous bleeding manifestations. Severe bleeding in ITP is not completely related with low platelet count. Thus, there is a great need for reliable indicators of the susceptibility of bleeding in ITP patients. Interleukin‐37 (IL‐37) is an anti‐inflammatory cytokine that participates in the process of several inflammatory and autoimmune diseases. However, the role of IL‐37 in the pathogenesis of ITP is unknown.Aims:Our study aimed to evaluate the regulatory role of IL‐37 in the process of ITP and its association with disease severity.Methods:Plasma IL‐37 was detected by enzyme‐linked immunosorbent assay (ELISA). We cultured the monocytes/macrophages from ITP patients to investigate the regulatory role of IL‐37 on monocytes/macrophages. Fcγ receptors (FcγRs) of macrophages were analyzed using flow cytometry and q‐PCR. Signaling pathways were determined by western blotting. Phagocytic capacity of macrophages was measured by the engulfment of opsonized platelets.Results:Plasma and mRNA levels of the anti‐inflammatory cytokine IL‐37 were elevated in ITP patients with platelet counts below 30 × 109 /L compared to healthy controls and to ITP patients with platelet counts above 30 × 109 /L. Furthermore, plasma IL‐37 levels correlated with the platelet number and IBLS bleeding scores of ITP patients. Specifically, ITP patients with skin and oral bleeding symptoms had higher plasma IL‐37 levels than patients without these bleeding symptoms. Patients with more severe skin and oral bleeding exhibited higher plasma IL‐37 levels, indicating that IL‐37 could be a candidate in evaluating disease severity of ITP. IL‐37 initiated an anti‐inflammatory effect on monocytes/macrophages from ITP patients by down‐regulating the phosphorylation of MAPK, AKT, and NF‐κB signaling pathways, which are pivotal in mediating inflammation. Moreover, IL‐37 restored the balance of activating and inhibitory FcγRs (Figure 1) and decreased antibody‐mediated platelet phagocytosis by monocytes/macrophages, suggesting that IL‐37 might be a potential therapeutic agent in ITP.Summary/Conclusion:Our study demonstrated that ITP patients exhibited higher IL‐37 expression, especially patients with severe hemorrhage or low platelet count. IL‐37 decreased antibody‐mediated platelet phagocytosis, restored the balance of activating and inhibitory FcγRs, and inhibited inflammatory activity via MAPK, AKT, and NF‐κB signaling pathways among monocytes/macrophages. Therefore, IL‐37 might be a candidate in evaluating the severity of ITP and a promising therapeutic agent for the management of ITP.image