THE IMMUNOSUPPRESSIVE MODE OF ACTION OF MIZORIBINE

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Abstract
Mizoribine (MIZ) suppressed the mitogen response and mixed [human] lymphocyte reaction (MLR) significantly at doses of 100 .mu.g/ml and 10 .mu.g/ml in a dose-response analysis. The 50% inhibition dose (ID50) was between 10 .mu.g/ml and 1.0 .mu.g/ml, both in the mitogen response and MLR. In a kinetic study of the MLR, the degree of suppression with MIZ at a given dosage was essentially the same as the degree of suppression observed in the dose-response analysis when MIZ was added to MLR cultures from day 0 to day 4. In addition, MLR was more susceptible to the suppressive activity of MIZ at 100 .mu.g/ml when MIZ was added near the peak of lymphocyte proliferation. MLR suppression induced by MIZ at 10 .mu.g/ml was reversible and MLR activity had completely recovered 6-8 h after its removal. MIZ had no inhibitory action on MLR-derived cytotoxic cells or the effector phase of cell mediated lymphocytotoxicity. MIZ suppresses lymphoproliferation, but has no effect on the recognition phase or effector phase of cytotoxic lymphocytes.

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