Immunosuppressive effects of (2R,5R)-6-heptyne-2,5-diamine an inhibitor of polyamine synthesis: I. Effects on mitogen-induced immunoglobulin production in human cultured lymphocytes.

Abstract

The consequences of specific inhibition of polyamine biosynthesis by (2R,5R)-6-heptyne-2,5-diamine (MAP) a potent inhibitor of L-ornithine decarboxylase (ODC), on immunoglobulin (Ig) production were studied in cultured human peripheral blood lymphocytes stimulated with pokeweed mitogen (PWM). MAP inhibits the usual PWM-induced increase of polyamine (putrescine, spermidine and spermine) concentrations and reduces concomitantly cell replication. In parallel with these biochemical effects, IgG and IgM production are diminished, a 95% decrease being observed at 100 microM MAP concentration. That the suppressive effects of the ODC inhibitor result from polyamine deficiency, and not from unrelated pharmacological effects, is demonstrated by the restoration of normal Ig production when 10 microM putrescine or spermidine are added to the culture medium. These findings established that the cellular immunological response can be affected by specific inhibition of polyamine biosynthesis and deserve further consideration both under in vitro and in vivo conditions.