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

Yalinbas E. E., SEZGİN EVİM M., Bor O., Gulbas Z.

JOURNAL OF PEDIATRIC HEMATOLOGY ONCOLOGY, vol.41, no.7, pp.574-578, 2019 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 41 Issue: 7
  • Publication Date: 2019
  • Doi Number: 10.1097/mph.0000000000001366
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Page Numbers: pp.574-578
  • Keywords: acute ITP, cytokines, P-glycoprotein, glucocorticoid receptor expression, apoptosis, megadose methylprednisolone, REGULATORY T-CELLS, MOLECULAR-MECHANISMS, PURPURA, RESISTANCE, LYMPHOCYTES, PATHOGENESIS, MANAGEMENT, SELECTION
  • Bursa Uludag University Affiliated: Yes


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-gamma, 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/mm(3) 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-gamma 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-gamma percentages compared with the control group (P<0.05). Th IL-2 and IFN-gamma percentages were significantly lowered with MDMP treatment (P<0.05). IFN-gamma/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.