Studies on the Suppression of Immune Responses by the Periwinkle Alkaloids Vincristine and Vinblastine*

Abstract

The " dimeric alkaloids vincristine and vinblastine, derived from the periwinkle plant Vinca rosea, were potent immunosuppressive agents in the rat. When administered at the time of immunization with bovine serum albumin in complete Freund''s adjuvant, antibody formation and delayed hypersensitivity to bovine serum albumin is completely suppressed, and hypersensitivity to tuberculin is markedly reduced. At high vincristine dosage, established delayed hypersensitivity to these antigens was promptly and regularly abolished, early antibody formation ceased, and homograft rejection was substantially delayed. Lesser degrees of inhibition of the inflammatory response to turpentine and Arthus reactivity were seen, and hair growth stopped when the drug was administered. A profound and consistent depression of small, medium, or large lymphocytes in the peripheral blood was not observed during immune suppression with vincristine. It was felt that the mechanism of the immunosuppressive action of vincristine most likely involved inhibition of the proliferation of one or more immunologically competent lymphoid cells, probably through a deoxyribonucleic acid (DNA) mechanism.