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Effect of cyclophosphamide on the immune response of BALB/c mice bearing an immunoglobulin M plasmacytoma (TEPC-183).

Mice bearing TEPC-183, an immunoglobulin (M(kappa)-secreting plasmacytoma, exhibit severe suppression of their immune responses. Since chemotherapy with cyclophosphamide (CY) is used in the treatment of myeloma, the present study was undertaken to determine its effect on the immune response. CY was tested at different doses in order to establish whether a tumor-lytic dose could be established which would minimally impair the immune response. In addition, CY was injected at different time intervals in respect to antigen administration, and its short- and long-term effects on the immune response were determined. It was found that 1 mg CY suppressed the six-day primary immune response to the type 3 pneumococcal polysaccharide SSS-III, and even a secondary response 30 days later. Three mg CY were required to suppress the primary as well as the secondary immune response elicited by 2,4-dinitrophenyl-hemocyanin. One injection of 1 mg CY per mouse resulted in complete regression of all tumors. Splenectomy did not aid in the recovery of the immune response to SSS-III but accentuated the impairment. The time of CY administration played a crucial role in affecting the immune response. When CY was administered simultaneously with or two days after antigen injection, it was totally suppressive, whereas the immune response was enhanced when CY was given four days prior to antigen injection. Minimal effects were observed when CY was given at other time intervals.