Increased spontaneous immunoglobulin secretion associated with cyclophosphamide-induced immune suppression.
Spontaneous immunoglobulin (Ig) secretion by cells from multiple sclerosis (MS) patients (in the progressive phase) treated with monthly pulse doses of cyclophosphamide (CY) (1000-1600 mg/M2) was measured using the protein A plaque assay, to evaluate the effect of CY treatment on B-cell function. Surprisingly, an increase, rather than a decrease, in Ig-secreting cells was seen following CY treatment. CY-treated MS patients averaged 1380 +/- 535 spontaneous total (IgM + G + A) Ig plaque-forming cells (PFC) per 1 X 10(6) peripheral blood mononuclear cells (MNC), measured at 15-22 days after monthly CY administration, while healthy adults had 280 +/- 47 Ig PFC/10(6) MNC, and MS patients not treated with CY had 300 +/- 43 Ig PFC/10(6) MNC. The observed increase was due to an increase in IgG and IgA PFC. PFC levels remained elevated for 4 weeks following CY treatment, decreasing to control levels by 7-8 weeks post-CY. A small increase in serum IgG level was noted after greater than 12 months of pulse CY therapy; no increase was seen in CSF IgG levels. A preferential decrease in the number of CD4+ T cells was also seen in the CY-treated MS patients. We propose that the observed increase in the number of spontaneous Ig PFC was due to the CY-induced disruption of the CD4+ T cell-mediated control of in vivo activated B cells.
D000921:Antibody-Producing Cells / Q000187:drug effects / Q000276:immunology; D003520:Cyclophosphamide / Q000627:therapeutic use*; D006801:Humans; D007074:Immunoglobulin G / Q000134:cerebrospinal fluid / Q000378:metabolism; D007136:Immunoglobulins / Q000096:biosynthesis*; D007165:Immunosuppression Therapy; D007700:Kinetics; D007958:Leukocyte Count; D008214:Lymphocytes / Q000145:classification / Q000187:drug effects / Q000276:immunology; D009103:Multiple Sclerosis / Q000097:blood / Q000188:drug therapy* / Q000276:immunology
D007074:Immunoglobulin G; D007136:Immunoglobulins; D003520:Cyclophosphamide