Polyamine deprivation prevents the development of tumour-induced immune suppression.
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.
Chamaillard
L
L
Groupe de Recherche en Thérapeutique Anticancéreuse, URA CNRS 1529, Affiliée INSERM, Institut de Recherche Contre le Cancer (IRCC), Rennes, France.
Catros-Quemener
V
V
Delcros
J G
JG
Bansard
J Y
JY
Havouis
R
R
Desury
D
D
Commeurec
A
A
Genetet
N
N
Moulinoux
J P
JP
D000818:Animals; D018827:Carcinoma, Lewis Lung / Q000276:immunology*; D015232:Dinoprostone / Q000097:blood; D000518:Eflornithine / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007108:Immune Tolerance; D007376:Interleukin-2 / Q000096:biosynthesis*; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D009368:Neoplasm Transplantation; D009929:Organ Size; D000587:Oxidoreductases Acting on CH-NH Group Donors / Q000037:antagonists & inhibitors; D011073:Polyamines / Q000378:metabolism*; D011700:Putrescine / Q000031:analogs & derivatives / Q000494:pharmacology; D013154:Spleen / Q000033:anatomy & histology / Q000166:cytology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D000097667:Polyamine Oxidase
D015232:Dinoprostone; D000518:Eflornithine; D004791:Enzyme Inhibitors; D007376:Interleukin-2; D000587:Oxidoreductases Acting on CH-NH Group Donors; D011073:Polyamines; D011700:Putrescine; D000097667:Polyamine Oxidase; C044445:MDL 72527