CHRONIC ADMINISTRATION OF DEXAMETHASONE RESULTS IN FC RECEPTOR UP-REGULATION AND INHIBITION OF CLASS-I ANTIGEN EXPRESSION ON MACROPHAGES FROM MRL LPR AUTOIMMUNE MICE/

The MRL/lpr mouse develops, after approximately 8 weeks of age, a seve re autoimmune syndrome with many features resembling human systemic lu pus erythematosus, including autoantibodies against DNA and basement m embranes resulting in immune complexes, vasculitis, and multiorgan dis ease. While this murine model of lupus has been used for the identific ation of therapeutics with potential efficacy in human autoimmune dise ase, the long-term impact of chronic immunosuppressive therapy on macr ophage function in this paradigm is not understood, To this end, MRL/l pr mice were treated prophylactically with dexamethasone at 0.01, 0.1, and 1 mg/kg of body weight for 20 weeks or were allowed to develop au toimmune disease and, at 15 weeks of age, treated therapeutically with 1-mg/kg dexamethasone for 8 additional weeks, Analysis of surface ant igens on resident peritoneal macrophages demonstrated a progressive lo ss in class I expression with a concomitant increase in Fe receptor ex pression, Neither phagocytosis nor CD11b expression was modulated with chronic steroid treatment, Furthermore, dexamethasone treatment was a ssociated with a reduction in anti-DNA antibodies and total immunoglob ulin G and yet an elevation in serum cholesterol due to an increase in high-density lipoproteins. Therefore, the MRL/lpr mouse serves not on ly as a small-animal model of autoimmune disease but also as one in wh ich the negative and positive sequelae associated with chronic immunos uppression can be further understood.