Effects of whole body X-irradiation and cyclophosphamide treatment on induction of macrophage tumoricidal function in mice

The influence of whole body X-irradiation (200–800 R) and subcutaneous cyclophosphamide (CY) treatment (150–500 mg/kg) was studied on the ability of adjuvants to induce cytotoxic macrophages in vivo. Surprisingly, radiation or CY therapy alone produced growth inhibitory macrophages whose function peaked within 2 days after treatment. When adjuvants such as Bacillus Calmette Guérin (BCG), pyran copolymer, or glucan were administered ip within 2 hr after sublethal (600 R) X-irradiation, adjuvant-induced cytotoxic function was depressed but not ablated. In addition, when noninduced peritoneal macrophages were obtained 6 days after lethal (800 R) X-irradiation, their ability to be activated in vitro by lymphokine or fibroblast-derived interferon preparations was only slightly depressed at all concentrations of inducer tested. When BCG, pyran, or glucan was administered ip concurrently with sc CY treatment, only the ability of BCG to activate macrophages was markedly reduced, indicating separate mechanisms for the induction of tumoricidal macrophages. A better understanding of the interaction of chemotherapeutic and/or radiation regimens with adjuvants which affect macrophage function may be instrumental to rationalized immunotherapy protocols.