Correction of Th1-dominant Cytokine Profiles by High-dose Dexamethasone in Patients with Chronic Idiopathic Thrombocytopenic Purpura Authors
First Online: 06 July 2007 Received: 02 March 2007 Accepted: 06 June 2007 DOI:
Cite this article as: Guo, C., Chu, X., Shi, Y. et al. J Clin Immunol (2007) 27: 557. doi:10.1007/s10875-007-9111-1 Abstract
To investigate the possible correcting of T helper (Th) cytokine profiles by high-dose dexamethasone (HD-DXM) therapy in chronic idiopathic thrombocytopenic purpura (ITP) with active disease, we determined the plasma levels of IFN-γ, IL-2, IL-4, IL-10, and TGF-β1 in 52 patients before and after oral administration of 40 mg/day DXM for four consecutive days. The cytokine levels were measured by enzyme-linked immunosorbent assay. The results showed that initial responses were reached in all patients and sustained response (SR) rate is 46.15%. The pretreatment plasma levels of both IFN-γ and IL-2 were significantly increased and those of IL-4, IL-10, and TGF-β1 significantly decreased, compared with those of the normal controls (
P < 0.01), indicating a Th1-dominant cytokine profile typically found in ITP. After HD-DXM treatment, IFN-γ and IL-2 were decreased ( P < 0.01), whereas IL-4 and IL-10 were increased ( P < 0.05). There was no significant difference between the HD-DXM-treated patients and the normal controls ( P > 0.05). TGF-β1 was also increased ( P < 0.01) after HD-DXM treatment, but still lower than that of the normal controls ( P < 0.05). During following-up, the cytokine profiles in the SRs remained stable compared to the posttreatment level ( P > 0.05), but IFN-γ and IL-2 levels raised up, and IL-4, IL-10, and TGF-β1 levels reduced again in the relapsed patients ( P < 0.01). Our data demonstrate that HD-DXM is an effective initial therapy for ITP, and the Th1 cytokine dominance could be corrected by HD-DXM. Keywords Idiopathic thrombocytophenic purpura cytokines T helper lymphocyte dexamethasone References
Kuwana M, Kaburaki J Ikeda Y. Autoreactive T cells to platelet GPIIb-IIIa in immune thrombocytopenic purpura: role in production of anti-platelet autoantibody. J Clin Invest 1998;102:1393–402.
Hedlund-Treutiger I, Wahlstrom J, Elinder G. Role of the T cell receptor in idiopathic thrombocytopenic purpura (ITP). Acta Paediatr Suppl 1998;424:46–50.
Semple JW, Lazarus AH, Freedman J. The cellular immunology associated with autoimmune thrombocytopenic purpura: an update. Transfus Sci 1998;19:245–51.
Cines DB, McMillan R. Management of adult idiopathic thrombocytopenic purpura. Annu Rev Med 2005;56:425–42.
Semple JW, Freedman J. Increased antiplatelet T helper lymphocyte reactivity in patients with autoimmune thrombocytopenia. Blood 1991;78:2619–25.
Garcia-Suarez J, Prieto A, Reye E, Manzano L, Merino JL, Alvarez-Mon M. The clinical outcome of autoimmune thrombocytopenic purpura is related to their T-cell immunodeficiency. Br J Haematol 1993;84:464–70.
Ware RE, Howard TA. Elevated numbers of gamma delta(γδ+)T lymphocytes in children with immune thrombocytopenic purpura. J Clin Immunol 1994;14:237–47.
Crossley AR, Dickinson AM, Proctor SJ, Calvert JE. Effects of interferon-á therapy on immune parameters in immune thrombocytopenic purpura. Autoimmunity 1996;24:81–100.
Erduran E, Aslan Y, Aliyazicioglu Y, Mocan H, Gedik Y. Plasma soluble interleukin-2 receptor levels in patients with idiopathic thrombocytopenic purpura. Am J Hematol 1998;57:119–23.
Ogawara H, Handa H, Morita K, Hayakawa M, Kojima J, Amagai H, et al. High Th1/Th2 ratio in patients with chronic autoimmune thrombocytopenic purpura. Eur J Haematol 2003;71:283–8.
Panitsas FP, Theodoropoulou M, Kouraklis A, Karakantza M, Theodorou GL, Zoumbos NC, et al. Adult chronic idiopathic thrombocytopenic purpura (ITP) is the manifestation of a type-1 polarized immune response. Blood 2004;103:2645–7.
Wali YA, Al Lamki Z, Shah W, Zacharia M, Hassan A. Pulsed high-dose dexamethasone therapy in children with chronic idiopathic thrombocytopenic purpura. Pediatr Hematol Oncol 2002;19:329–35.
Cheng Y, Wong RS, Soo YO, Chui CH, Lau FY, Chan NP, et al. Initial treatment of immune thrombocytopenic purpura with high-dose dexamethasone. N Engl J Med 2003;349:831–6.
Borst F, Keuning JJ, van Hulsteijn H, Sinnige H, Vreugdenhil G. High-dose dexamethasone as a first- and second-line treatment of idiopathic thrombocytopenic purpura in adults. Ann Hematol 2004;83:764–8.
George JN, Woolf SH, Raskob GE. Idiopathic thrombocytopenic purpura: a guideline for diagnosis and management of children and adults. American Society of Hematology. Ann Med 1998;30:38–44.
British Committee for Standards in Haematology. General Haematology Task Force: Guidelines for the investigation and management of idiopathic thrombocytopenic purpura in adults, children and in pregnancy. Br J Haematol 2003;120:574–96.
Gutierrez-Espindola GR, Morales-Polanco MR, Guerrero-Rivera S, Talavera JO, Sanchez-Valle E, Gomez-Morales E, et al. High doses of dexamethasone in adult patients with idiopathic thrombocytopenic purpura. Arch Med Res 2003;34:31–4.
Mazzucconi MG, Fazi P, Bernasconi S, De Rossi G, Leone G, Gugliotta L, et al. Therapy with high-dose dexamethasone (HD-DXM) in previously untreated patients affected by idiopathic thrombocytopenic purpura. A GIMEMA experience. Blood 2007;109(4):1401–7.
Andersson J. Cytokines in idiopathic thrombocytopenic purpura (ITP). Acta Paediatr Suppl 1998;424:61–4.
Yoshimura C, Nomura S, Nagahama M, Ozaki Y, Kagawa H, Fukuhara S. Plasma-soluble Fas (APO-1, CD95) and soluble Fas ligand in immune thrombocytopenic purpura. Eur J Haematol 2000;64:219–24.
Andersson PO, Stockelberg D, Jacobsson S, Wadenvik H. A transforming growth factor-beta1-mediated bystander immune suppression could be associated with remission of chronic idiopathic thrombocytopenic purpura. Ann Hematol 2000;79:507–13.
Andersson PO, Olsson A, Wadenvik H. Reduced transforming growth factor-beta1 production by mononuclear cells from patients with active chronic idiopathic thrombocytopenic purpura. Br J Haematol 2002;116:862–7.
Jackson M, Ahmad Y, Bruce IN, Coupes B, Brenchley PE. Activation of transforming growth factor-beta1 and early atherosclerosis in systemic lupus erythematosus. Arthritis Res 2006;8:R81.
Agarwal SK, Marshall GD Jr. Dexamethasone promotes type 2 cytokine production primarily through inhibition of type 1 cytokines. J Interferon Cytokine Res 2001;21:147–55.
Wang T, Zhao H, Ren H, Guo J, Xu M, Yang R, et al. Type 1 and type 2 T-cell profiles in idiopathic thrombocytopenic purpura. Haematologica 2005;90:914–23.
Adcock IM, Brown CR, Gelder CM, Shirasaki H, Peters MJ, Barnes PJ. The effects of glucocorticoids on transcription factor activation in human peripheral blood mononuclear cells. Am J Physiol 1995;37:C331.
Peng J, Liu CF, Liu D, Ren C, Li W, Wang Z, et al. Effects of B7-blocking agent and/or CsA on induction of platelet-specific T-cell anergy in chronic autoimmune thrombocytopenic purpura. Blood 2003;101:2721–6.
DeKruyff RH, Fang Y, Umetsu DT. Corticosteroids enhance the capacity of macrophages to induce Th2 cytokine synthesis in CD4
lymphocytes by inhibiting IL-12 production. J Immunol 1998;160:2231–7.
PubMed Copyright information
© Springer Science+Business Media, LLC 2007