POLYAMINE DEPRIVATION PREVENTS THE DEVELOPMENT OF TUMOR-INDUCED IMMUNE SUPPRESSION

Mice grafted with the 3LL (Lewis lung) carcinoma exhibit immune suppre ssion: spleen cells showed decreased spontaneous interleukin 2 (IL-2) production and T-CD4(+) and T-CD8(+) lymphocyte populations; in additi on the polyamine content in the spleen was increased. By treating the mice with a polyamine-deficient diet containing neomycin, metronidazol e and inhibitors of ornithine decarboxylase and polyamine oxydase, tum our growth was reduced and the immune abnormalities were reversed. The spleen cells overproduced IL-2 by reducing exogenous sources of polya mines, but total blockade of all major polyamine sources was necessary to obtain an optimal effect both on IL-2 production and on spleen pol yamine content. Irrespective of whether polyamine deprivation was star ted at an early or at an advanced stage of tumour growth, T-lymphocyte populations were restored to normal values, demonstrating that polyam ine deprivation not only prevents tumour-induced immune suppression, b ut reverses established immunological disorders. In contrast to what w as observed regarding IL-2 production by spleen cells and natural kill er (NK) cell activity, the polyamine oxidase (PAO) inhibitor did not e nhance the number of T lymphocytes. These findings are consistent with a direct effect of the polyamines on immune effector cell metabolism. They suggest an important role of the gastrointestinal polyamines and of PAO activity in the regulation of IL-2 production.