INTRAVENOUS CYCLOPHOSPHAMIDE COMBINED WITH METHYLPREDNISOLONE IN THE TREATMENT OF SEVERE REFRACTORY RHEUMATOID-ARTHRITIS - THE EFFECT ON LYMPHOCYTES

The mode of action of methylprednisolene and cyclophosphamide in the t reatment of rheumatoid arthritis still remains unclear. We sought to d etermine whether methylprednisolone and/or cyclophosphamide affect sur face antigens on peripheral blood lymphocytes. Twenty-eight patients w ith severe refractory rheumatoid arthritis were observed for 12 months . Thirteen patients were treated with an intravenous pulse of methylpr ednisolone, and fifteen with methylprednisolone combined with cyclopho sphamide. The surface antigens of lymphocytes and natural killer (NK) cells isolated from peripheral blood were determined using flowcytomet ry. The clinical improvement was observed in 16 (57%) patients (8 trea ted with methylprednisolone and 8 with methylprednisolone/cyclophospha mide). However, after cessation of the treatment in 9 patients, a flar e up of the disease was observed. A striking decrease in total lymphoc yte count was observed. The percentage of CD3+ and CD3+CD4+ cells rema ined unchanged. We observed a decrease in the percentage of CD3+CD8+ i n patients treated with methylprednisolone/cyclophosphamide. Moreover, the percentage of activated T cells (CD25+ cells and HLA-DR+ cells) w as reduced. The depletion of CD8+CD25+ cells was observed after combin ed treatment. The percentage of CD19+CD5+ was reduced due to the treat ment We also observed a decrease in CD16+CD56+ NK cells. Amelioration of the course of the refractory rheumatoid arthritis was observed in p atients treated with both methylprednisolone and methylprednisolone/cy clophosphamide. A stronger effect on lymphocyte phenotype was observed in those given methylprednisolone/cyclophosphamide, but it was not fo llowed by further benefit. On the other hand, the clinical improvement was more stable in methylprednisolone/cyclophosphamide-treated patien ts. The use of cyclophosphamide should be reserved for patients with r apidly progressing rheumatoid arthritis or life-threatening complicati ons.