Is steroid resistance related to multidrug resistance-I (MDR-I) in rheumatoid arthritis?
Both healthy ageing and rheumatoid arthritis (RA) are frequently associated with acquired steroid resistance. Here, we investigated the potential involvement of steroid resistance with multidrug resistance (MDR) and explored the impact of pathological ageing on lymphocyte sensitivity to glucocorticoids. Seventy-four RA patients and 26 healthy controls took part in this study. Peripheral blood mononuclear cells were isolated and T-cell sensitivity to glucocorticoids was measured in vitro. The functional activity of P-glycoprotein was analyzed by flow cytometry and ABCB1/MDR-1 gene polymorphisms were assessed in peripheral lymphocytes. Patients and controls had similar sensitivities to glucocorticoids. Only controls presented age-related immunological changes, including reduced T-cell proliferation and relative resistance to corticosterone. Patients had a higher percentage (72%) of lymphocytes actively extruding rhodamine 123 (Rh123(dim)) than controls (60%) in spite of similar P-glycopr