Intravenous cyclophosphamide combined with methylprednisolone in the treatment of severe refractory rheumatoid arthritis: the effect on lymphocytes.
The mode of action of methylprednisolone and cyclophosphamide in the treatment of rheumatoid arthritis still remains unclear. We sought to determine whether methylprednisolone and/or cyclophosphamide affect surface antigens on peripheral blood lymphocytes. Twenty-eight patients with severe refractory rheumatoid arthritis were observed for 12 months. Thirteen patients were treated with an intravenous pulse of methylprednisolone, and fifteen with methylprednisolone combined with cyclophosphamide. The surface antigens of lymphocytes and natural killer (NK) cells isolated from peripheral blood were determined using flow cytometry. The clinical improvement was observed in 16 (57%) patients (8 treated with methylprednisolone and 8 with methylprednisolone/cyclophosphamide). However, after cessation of the treatment in 9 patients, a flare up of the disease was observed. A striking decrease in total lymphocyte count was observed. The percentage of CD3+ and CD3+CD4+ cells remained unchanged. We observed a decrease in the percentage of CD3+CD8+ in patients treated with methylprednisolone/cyclophosphamide. Moreover, the percentage of activated T cells (CD25+ cells and HLA-DR+ cells) was reduced. The depletion of CD8+CD25+ cells was observed after combined treatment. The percentage of CD19+CD5+ was reduced due to the treatment. We also observed a decrease in CD16+CD56+ NK cells. Amelioration of the course of the refractory rheumatoid arthritis was observed in patients treated with both methylprednisolone and methylprednisolone/cyclophosphamide. A stronger effect on lymphocyte phenotype was observed in those given methylprednisolone/cyclophosphamide, but it was not followed by further benefit. On the other hand, the clinical improvement was more stable in methylprednisolone/cyclophosphamide-treated patients. The use of cyclophosphamide should be reserved for patients with rapidly progressing rheumatoid arthritis or life-threatening complications.
Lacki
J K
JK
Department of Rheumatology, Karol Marcinkowski University School of Medicine, Poznan, Poland.
Leszczynski
P
P
Mackiewicz
S H
SH
D000328:Adult; D015703:Antigens, CD / Q000187:drug effects / Q000276:immunology; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007275:Injections, Intravenous; D008214:Lymphocytes / Q000187:drug effects* / Q000276:immunology; D008297:Male; D008775:Methylprednisolone / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use*; D008875:Middle Aged
D015703:Antigens, CD; D003520:Cyclophosphamide; D008775:Methylprednisolone