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Cytokine Profile, Apoptosis, Glucocorticoid Receptor, and P-glycoprotein Expression Before and After Megadose Methylprednisolone Treatment in Children With Acute Immune Thrombocytopenia

Yalinbaş, Emine E. MD*; Sezgin Evim, Melike MD; Bör, Özcan MD; Gülbaş, Zafer MD§

Journal of Pediatric Hematology/Oncology: November 28, 2018 - Volume Publish Ahead of Print - Issue - p
doi: 10.1097/MPH.0000000000001366
Clinical and Laboratory Observations: PDF Only

Objective: Immune thrombocytopenia (ITP) is an autoimmune disease, and it has become evident that T lymphocytes play an important role in the pathogenesis of ITP. We investigated the role of T helper (Th) intracellular IL-2, IL-4, IL-6, IFN-γ, and T lymphocyte apoptosis in the pathogenesis of acute ITP and the effect of glucocorticoid treatment on cytokine profile. We investigated also P-glycoprotein (P-gp) and glucocorticoid receptor (GCR) expression as a possible mechanism for glucocorticoid resistance.

Material and Methods: The study includes 20 children with acute ITP having a platelet count <20,000/mm3 and 20 healthy children as a control group. Patients with acute ITP were treated with megadose methylprednisolone (MDMP) (MDMP in the dose of 30 mg/kg/d between day 1 and 3 and 20 mg/kg/d between day 4 and 7). Th intracellular IL2, IL-4, IL-6, and IFN-γ percentages, T-cell P-gp expression, T-cell and monocyte GCR expression, and T-cell apoptosis were evaluated before and after treatment in acute ITP patients and in the control group.

Results: Acute ITP patients had significantly higher Th IL-2, IL-4, IL-6, and IFN-γ percentages compared with the control group (P<0.05). Th IL-2 and IFN-γ percentages were significantly lowered with MDMP treatment (P<0.05). IFN-γ/IL-4 ratio was also lowered with the MDMP treatment (P<0.05). T-lymphocyte P-gp expression and T lymphocyte and monocyte GCR expression were all similar between acute ITP pretreatment and control groups (P>0.05). T-lymphocyte P-gp expression was higher in the posttreatment group than in the pretreatment group (P<0.05). Both T lymphocyte and monocyte GCR expression percentages were not different in the pretreatment and posttreatment groups (P>0.05). Early apoptosis in T lymphocytes was significantly lower in the pretreatment acute ITP group than in the control group (P<0.05). Necrotic apoptosis in T lymphocytes was significantly increased with MDMP treatment (P<0.05).

Conclusions: Th1 and Th2 cytokine profile is observed in acute ITP pathogenesis, and MDMP treatment causes Th1 to Th2 cytokine profile shift and induction of T-lymphocyte apoptosis. There is a need to have a greater number of resistant cases in order to better evaluate the P-gp and GCR expression in glucocorticoid resistance in acute ITP.

*Department of Neonatology, Dumlupinar University Medical Faculty, Kütahya

Department of Pediatric Hematology, Uludag University Medical Faculty, Bursa

Department of Pediatric Hematology, Eskişehir Osmangazi University Medical Faculty, Eskişehir

§Department of Hematology, Anadolu Sağlik Merkezi (Private Hospital/In affiliation with Johns Hopkins Medicine), Gebze, Turkey

The authors declare no conflict of interest.

Reprints: Melike Sezgin Evim, MD, Department of Pediatric Hematology, Uludag University Medical Faculty, Bursa 16059, Turkey (e-mail:

Received March 1, 2018

Accepted October 21, 2018

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