Comparative effects of azathioprine, cyclophosphamide and frentizole on cellular immunity in mice

This report extends previous observations on the immunosuppressive properties of cyclophosphamide (CPA), azathioprine and frentizole (15) to include murine models of cellular immunity. Systemic and local graft vs host reactions (GVHR) were most effectively suppressed by CPA. In contrast to frentizole, both CPA and azathioprine were found to inhibit the proliferation of parental T-cells in a systemic GVHR. However, CPA was the only agent capable of inhibiting the proliferation of T-cells following contact sensitization with oxazolone. Mice pretreated with a high dose of CPA or frentizole prior to inoculation with the murine sarcoma virus exhibited accelerated tumor growth. However, there was no accelerated growth of murine sarcoma virus induced tumors or an SaI spindle cell fibrosarcoma during rather prolonged therapy with immunosuppressive doses of CPA, azathioprine or frentizole. Normal mice treated with CPA showed a more drastic reduction in lymphoid elements of the spleen and thymus than mice treated with azathioprine or frentizole. Studies on the mitogenic responsiveness of spleen cells obtained from normal mice after an eight day course of therapy suggested that CPA has some selectivity of action on B-cells and azathioprine on T-cells.