Study on the relationship of tumor necrosis factor-α and glucocorticoid-resistant idiopathic thrombocytopenia purpura

Objective To study the expression of tumor necrosis factor-alpha(TNF-α) in idiopathic thrombocytopenia purpura(ITP) patients and the effect of TNF-α on the expression of human glucocorticoid receptor(GR) in order to explore the relationship of TNF-α and glucocorticoid resistance.Methods The plasma TNF-α concentrations were measured by enzyme-linked immunosorbent assay(ELISA) in glucocorticoid sensitive and glucocorticoid resistant ITP patients.Human peripheral blood mononuclear cells(PBMC)from healthy volunteers were isolated and the mRNA expressions and protein expressions of GRα and GRβ in PBMC being cultured with TNF-α were detected by RT-PCR and Western blot.Results The plasma TNF-α concentrations in ITP groups were significantly higher than that in controls(P0.01).The plasma TNF-α concentrations in the glucocorticoid resistant group was significantly higher than that in the glucocorticoid sensitive group(P0.05).After being cultured with TNF-α for 24 h,the expression of hGRα mRNA in PBMC of the cultured group was identical to that of the controls(P0.05),which GRα/GAPDH mRNA of the cultured group and the controls were 1.16±0.73 and 1.20±0.51,respectively.But the expression of hGRβ mRNA in the cultured group was significantly higher than that in the controls(P0.05),the GRβ/GAPDH mRNAs of the cultured group and the controls were 1.62±0.59 and 0.81±0.66,respectively.The GRα protein expressions were similar in both groups,but the GRβ protein expression in TNF-α-stimulated group was higher than that in the controls.Conclusion The plasma TNF-α concentrations were significantly higher in the glucocorticoid resistant ITP patients.TNF-α can increase the expression of GRβ,which may be one of the mechanisms of glucocorticoid resis-tance induced by inflammatory cytokines.