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. 1997;76(3):365–370. doi: 10.1038/bjc.1997.391

Polyamine deprivation prevents the development of tumour-induced immune suppression.

L Chamaillard 1, V Catros-Quemener 1, J G Delcros 1, J Y Bansard 1, R Havouis 1, D Desury 1, A Commeurec 1, N Genetet 1, J P Moulinoux 1
PMCID: PMC2224072  PMID: 9252204

Abstract

Mice grafted with the 3LL (Lewis lung) carcinoma exhibit immune suppression: spleen cells showed decreased spontaneous interleukin 2 (IL-2) production and T-CD4+ and T-CD8+ lymphocyte populations; in addition the polyamine content in the spleen was increased. By treating the mice with a polyamine-deficient diet containing neomycin, metronidazole and inhibitors of ornithine decarboxylase and polyamine oxydase, tumour growth was reduced and the immune abnormalities were reversed. The spleen cells overproduced IL-2 by reducing exogenous sources of polyamines, but total blockade of all major polyamine sources was necessary to obtain an optimal effect both on IL-2 production and on spleen polyamine content. Irrespective of whether polyamine deprivation was started at an early or at an advanced stage of tumour growth, T-lymphocyte populations were restored to normal values, demonstrating that polyamine deprivation not only prevents tumour-induced immune suppression, but reverses established immunological disorders. In contrast to what was observed regarding IL-2 production by spleen cells and natural killer (NK) cell activity, the polyamine oxidase (PAO) inhibitor did not enhance 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.

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Selected References

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