INTERLEUKIN-37 REDUCES INFLAMMATION AND IMPAIRS PHAGOCYTOSIS OF PLATELETS IN IMMUNE THROMBOCYTOPENIA
Author(s): ,
Yajing Zhao
Affiliations:
Haematology,Qilu Hosipital,Jinan,China
,
Guosheng Li
Affiliations:
Haematology,Qilu Hosipital,Jinan,China
,
Xinguang Liu
Affiliations:
Haematology,Qilu Hosipital,Jinan,China
,
Jun Peng
Affiliations:
Haematology,Qilu Hosipital,Jinan,China
Ming Hou
Affiliations:
Haematology,Qilu Hosipital,Jinan,China
EHA Library. Zhao Y. Jun 15, 2019; 267097; PS1480
Dr. Yajing Zhao
Dr. Yajing Zhao
Contributions
Abstract

Abstract: PS1480

Type: Poster Presentation

Presentation during EHA24: On Saturday, June 15, 2019 from 17:30 - 19:00

Location: Poster area

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.

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.

Session topic: 32. Platelets disorders

Keyword(s): Immune thrombocytopenia (ITP), Inflammation, Macrophage, Monocyte

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