Dose response curves for some immunosuppressive agents

Summary

Many immunosuppressive chemotherapeutic agents act largely through impairment of cell reproductive integrity. Using the Jerne's plaque assay, the inhibitory effect of nitrogen mustard, melphalan, 5-fluorouracil and 6-thioguanine on antibody formation was studied. It was observed that manipulation of the dose, frequency of administration and its timing in relation to immunization altered the magnitude of immunosuppression. In other experiments, the role of reticulo-endothelial system, thymic function and nutritional factors was found to be critical. For corresponding degrees of progressive immunosuppression, the dose of alkylating agents was increased in an arithmetic fashion and by log increments in the case of antimetabolites. There findings have relevance in formulating maximally effective therapeutic schedules with minimal toxicity.