Multidrug resistance-I (MDR-I) in rheumatic autoimmune disorders: Part I: Increased P-glycoprotein activity in lymphocytes from rheumatoid arthritis patients might influence disease outcomes [Phénotype MDR-I de multirésistance aux traitements de fond dans les maladies rhumatismales auto-immunes: Première partie : une activité accrue de la P-glycoprotéine lymphocytaire pourrait influencer l'évolution de la polyarthrite rhumatdïde] Article uri icon

abstract

  • Background. Multidrug resistance (MDR) is characterized by overexpression of P-glycoprotein, a pump molecule that decreases intracellular drug concentrations by increasing drug efflux from cells. Objective. To look for correlations between clinical status and P-glycoprotein activity and/or TNF-α mRNA levels in patients with rheumatoid arthritis. Methods. Sixteen patients were studied. Based on response to therapy, eight were refractory and eight nonrefractory to treatment. Findings were compared to those in 24 healthy controls. Flow cytometry was used to evaluate P-glycoprotein activity in peripheral blood mononuclear cells isolated by gradient centrifugation and incubated with the P-glycoprotein substrate daunorubicin. TNF-α mRNA levels were determined using quantitative PCR. Results. Patients with rheumatoid arthritis showed an increased number of lymphocytes with high P-glycoprotein activity (p = 0.0001) as compared to the normal controls. P-glycoprotein activity was higher in the refractory than in the non-refractory patient subgroup (p = 0.006). Also, TNF-α mRNA levels were markedly higher in the refractory subgroup than in the nonrefractory subgroup, and were undetectable in the normal controls. Conclusions. Enhanced P-glycoprotein activity may be closely related to an unfavorable clinical course and a poor response to treatment. Increased TNF-α expression and chronic exposure to various drugs, including glucocorticoids, may contribute to increase P-glycoprotein activity. Both high P-glycoprotein activity and excessive amounts of TNF-α seem associated with poor outcomes in rheumatoid arthritis. © 2000 %27Editions scientifiques et médicales Elsevier SAS. Tous droits réservés.
  • Background. Multidrug resistance (MDR) is characterized by overexpression of P-glycoprotein, a pump molecule that decreases intracellular drug concentrations by increasing drug efflux from cells. Objective. To look for correlations between clinical status and P-glycoprotein activity and/or TNF-α mRNA levels in patients with rheumatoid arthritis. Methods. Sixteen patients were studied. Based on response to therapy, eight were refractory and eight nonrefractory to treatment. Findings were compared to those in 24 healthy controls. Flow cytometry was used to evaluate P-glycoprotein activity in peripheral blood mononuclear cells isolated by gradient centrifugation and incubated with the P-glycoprotein substrate daunorubicin. TNF-α mRNA levels were determined using quantitative PCR. Results. Patients with rheumatoid arthritis showed an increased number of lymphocytes with high P-glycoprotein activity (p = 0.0001) as compared to the normal controls. P-glycoprotein activity was higher in the refractory than in the non-refractory patient subgroup (p = 0.006). Also, TNF-α mRNA levels were markedly higher in the refractory subgroup than in the nonrefractory subgroup, and were undetectable in the normal controls. Conclusions. Enhanced P-glycoprotein activity may be closely related to an unfavorable clinical course and a poor response to treatment. Increased TNF-α expression and chronic exposure to various drugs, including glucocorticoids, may contribute to increase P-glycoprotein activity. Both high P-glycoprotein activity and excessive amounts of TNF-α seem associated with poor outcomes in rheumatoid arthritis. © 2000 'Editions scientifiques et médicales Elsevier SAS. Tous droits réservés.

publication date

  • 2000-01-01