Multidrug resistance-I (MDR-I) in rheumatic autoimmune disorders - Part II: increased P-glycoprotein activity in lymphocytes from systemic lupus erythematosus patients might affect steroid requirements for disease control

Background. Over-expression of the membrane glycoprotein called P-glycoprot ein has been widely observed in a variety of both normal and neoplastic cel ls. P-glycoprotein is a pump molecule that transports hydrophobic drugs (in cluding steroids) and toxins outside the cell, thus inhibiting their therap eutic or toxic effects. The gene encoding P-glycoprotein is named multidrug resistance-1 (MDR-I). Objective. To evaluate the functional activity of P- glycoprotein in lymphocytes and monocytes from patients with systemic lupus erythematosus. Methods, 30 systemic lupus erythematosus patients and 20 he althy controls were studied. Peripheral blood mononuclear cells isolated by gradient centrifugation were incubated in the presence of daunorubicin (a fluorescent drug extruded by P-glycoprotein) at 37 degrees C or 4 degrees C for 30 min. P-glycoprotein activity was then analyzed using flow cytometry Results were expressed as the percentage of lymphocytes or monocytes with high P-glycoprotein activity (i.e., low fluorescence). Results. Mean fluore scence values for lymphocytes and monocytes were comparable between patient s and healthy controls. However, because our method allowed to measure P-gl ycoprotein, function at the single-cell level, we were able to show that th e mean percentage of lymphocytes with high P-glycoprotein activity was incr eased in the patients (11.51% +/- 14.3%) as compared to the healthy control s (0.71% +/- 0.57%) (P < 0.05). Moreover, P-glycoprotein activity was lower in the patients in clinical remission than in those with active disease. c onclusions, Our results suggest that P-glycoprotein function might affect g lucocorticoid requirements in systemic lupus erythematosus. (C) 2000 Editio ns scientifiques et medicales Elsevier SAS.