High-dose Dexamethasone Regulates Interleukin-18 and Interleukin-18 Binding Protein in Idiopathic Thrombocytopenic Purpura

Overview

Journal Haematologica

Specialty Hematology

Date 2009 Oct 3

PMID 19797730

Citations 12

Authors

Ning-Ning Shan

Xiao-Juan Zhu

Qian Wang

Chun-Yan Wang

Ping Qin

Jun Peng

Ming Hou

Affiliations

Soon will be listed here.

Abstract

To evaluate the effects of high-dose dexamethasone (HD-DXM) on the balance of interleukin-18 (IL-18) and its endogenous antagonist IL-18 binding protein (IL-18BP) in ITP patients, IL-18, IL-18BP as well as IFN-gamma, IL-4 plasma levels and platelet counts were determined in 17 ITP patients receiving DXM 40 mg/day for four consecutive days and in 24 healthy subjects. Using RT-PCR, the mRNA expression of IL-18, IL-18BP, IFN-gamma, IL-4, T-box (T-bet) and GATA-binding protein 3(GATA-3) were studied in all subjects. The in vitro effects of DXM on IL-18BP and IL-18 of peripheral blood mononuclear cells (PBMCs) were studied by ELISA. HD-DXM administration increased IL-18BP and reduced IL-18 expression significantly (p<0.05), which resulted in a downregulation of IL-18/IL-18BP ratio p<0.05). In vitro, DXM had a significant effect on secretion of IL-18BP while diminishing IL-18 release from cultures of PBMCs. These results suggest that downregulation of IL-18/IL-18BP might account for its clinical efficacy of HD-DXM in active ITP.

Citing Articles

The intellectual base and research fronts of IL-18: A bibliometric review of the literature from WoSCC (2012-2022).

Wang Z Cell Prolif. 2024; 57(11):e13684.

PMID: 39188114 PMC: 11533073. DOI: 10.1111/cpr.13684.

Interleukin-18 and IL-18BP in inflammatory dermatological diseases.

Wang X, Wang L, Wen X, Zhang L, Jiang X, He G Front Immunol. 2023; 14:955369.

PMID: 36742296 PMC: 9889989. DOI: 10.3389/fimmu.2023.955369.

Phytochemicals: Potential Therapeutic Modulators of Radiation Induced Signaling Pathways.

Jit B, Pradhan B, Dash R, Bhuyan P, Behera C, Behera R Antioxidants (Basel). 2022; 11(1).

PMID: 35052553 PMC: 8773162. DOI: 10.3390/antiox11010049.

Interleukin-18 and Hematopoietic Recovery after Allogeneic Stem Cell Transplantation.

Radujkovic A, Kordelas L, Bogdanov R, Muller-Tidow C, Beelen D, Dreger P Cancers (Basel). 2020; 12(10).

PMID: 32998441 PMC: 7601738. DOI: 10.3390/cancers12102789.

Interleukin-18 and miR-130a in severe sepsis patients with thrombocytopenia.

Cui Y, Wang B, Gao H, Xing Y, Li J, Li H Patient Prefer Adherence. 2016; 10:313-9.

PMID: 27042022 PMC: 4795447. DOI: 10.2147/PPA.S95588.

References

Gu Y, Kuida K, Tsutsui H, Ku G, Hsiao K, Fleming M . Activation of interferon-gamma inducing factor mediated by interleukin-1beta converting enzyme. Science. 1997; 275(5297):206-9. DOI: 10.1126/science.275.5297.206. View

Pfaffl M, Horgan G, Dempfle L . Relative expression software tool (REST) for group-wise comparison and statistical analysis of relative expression results in real-time PCR. Nucleic Acids Res. 2002; 30(9):e36. PMC: 113859. DOI: 10.1093/nar/30.9.e36. View

Adcock I, Brown C, Gelder C, Shirasaki H, Peters M, Barnes P . Effects of glucocorticoids on transcription factor activation in human peripheral blood mononuclear cells. Am J Physiol. 1995; 268(2 Pt 1):C331-8. DOI: 10.1152/ajpcell.1995.268.2.C331. View

Rodeghiero F . First-line therapies for immune thrombocytopenic purpura: re-evaluating the need to treat. Eur J Haematol Suppl. 2008; (69):19-26. DOI: 10.1111/j.1600-0609.2007.01000.x. View

. Guidelines for the investigation and management of idiopathic thrombocytopenic purpura in adults, children and in pregnancy. Br J Haematol. 2003; 120(4):574-96. DOI: 10.1046/j.1365-2141.2003.04131.x. View

Hurgin V, Novick D, Rubinstein M . The promoter of IL-18 binding protein: activation by an IFN-gamma -induced complex of IFN regulatory factor 1 and CCAAT/enhancer binding protein beta. Proc Natl Acad Sci U S A. 2002; 99(26):16957-62. PMC: 139251. DOI: 10.1073/pnas.262663399. View

Shan N, Zhu X, Peng J, Qin P, Zhuang X, Wang H . Interleukin 18 and interleukin 18 binding protein in patients with idiopathic thrombocytopenic purpura. Br J Haematol. 2008; 144(5):755-61. DOI: 10.1111/j.1365-2141.2008.07520.x. View

Cheng Y, Wong R, Soo Y, Chui C, Lau F, Chan N . Initial treatment of immune thrombocytopenic purpura with high-dose dexamethasone. N Engl J Med. 2003; 349(9):831-6. DOI: 10.1056/NEJMoa030254. View

Semple J, Freedman J . Increased antiplatelet T helper lymphocyte reactivity in patients with autoimmune thrombocytopenia. Blood. 1991; 78(10):2619-25. View

10.

McMillan R . Antigen-specific assays in immune thrombocytopenia. Transfus Med Rev. 1990; 4(2):136-43. DOI: 10.1016/s0887-7963(90)70258-1. View

11.

Ghayur T, Banerjee S, Hugunin M, Butler D, Herzog L, Carter A . Caspase-1 processes IFN-gamma-inducing factor and regulates LPS-induced IFN-gamma production. Nature. 1997; 386(6625):619-23. DOI: 10.1038/386619a0. View

12.

Coopamah M, Garvey M, Freedman J, Semple J . Cellular immune mechanisms in autoimmune thrombocytopenic purpura: An update. Transfus Med Rev. 2003; 17(1):69-80. DOI: 10.1053/tmrv.2003.50004. View

13.

DeKruyff R, Fang Y, Umetsu D . Corticosteroids enhance the capacity of macrophages to induce Th2 cytokine synthesis in CD4+ lymphocytes by inhibiting IL-12 production. J Immunol. 1998; 160(5):2231-7. View

14.

Mazzucconi M, Fazi P, Bernasconi S, De Rossi G, Leone G, Gugliotta L . Therapy with high-dose dexamethasone (HD-DXM) in previously untreated patients affected by idiopathic thrombocytopenic purpura: a GIMEMA experience. Blood. 2006; 109(4):1401-7. DOI: 10.1182/blood-2005-12-015222. View

15.

Panitsas F, Theodoropoulou M, Kouraklis A, Karakantza M, Theodorou G, Zoumbos N . Adult chronic idiopathic thrombocytopenic purpura (ITP) is the manifestation of a type-1 polarized immune response. Blood. 2003; 103(7):2645-7. DOI: 10.1182/blood-2003-07-2268. View

16.

Semple J, Milev Y, Cosgrave D, Mody M, Hornstein A, Blanchette V . Differences in serum cytokine levels in acute and chronic autoimmune thrombocytopenic purpura: relationship to platelet phenotype and antiplatelet T-cell reactivity. Blood. 1996; 87(10):4245-54. View

17.

Reddy P . Interleukin-18: recent advances. Curr Opin Hematol. 2004; 11(6):405-10. DOI: 10.1097/01.moh.0000141926.95319.42. View

18.

Peng J, Liu C, Liu D, Ren C, Li W, Wang Z . Effects of B7-blocking agent and/or CsA on induction of platelet-specific T-cell anergy in chronic autoimmune thrombocytopenic purpura. Blood. 2002; 101(7):2721-6. DOI: 10.1182/blood-2002-06-1666. View

19.

Guo C, Chu X, Shi Y, He W, Li L, Wang L . Correction of Th1-dominant cytokine profiles by high-dose dexamethasone in patients with chronic idiopathic thrombocytopenic purpura. J Clin Immunol. 2007; 27(6):557-62. DOI: 10.1007/s10875-007-9111-1. View