The effect of alpha-difluoromethylornithine, an inhibitor of polyamine biosynthesis, on mitogen-induced interleukin 2 production.
The objective of the present investigation was to examine the effect of DL-alpha-difluoromethylornithine (DFMO), an irreversible inhibitor of ornithine decarboxylase, on mitogen-induced interleukin 2 production. Treatment with DFMO reduced nylon wool T cell polyamine levels. In contrast, DFMO treatment enhanced, greater than two-fold, detectable levels of concanavalin A-induced interleukin 2 activity. This observed augmentation was not limited to in vitro DFMO treatment, since oral administration of DFMO to C57BL/6 mice also enhanced concanavalin A-induced interleukin 2 levels in vitro. Treatment with exogenous putrescine reversed the effect of DFMO on interleukin 2 levels. These results suggest that the effect of DFMO on interleukin 2 levels is mediated through polyamines. Therefore, polyamine biosynthesis may play a role in the intracellular regulation of interleukin 2 production.
D000818:Animals; D003208:Concanavalin A / Q000494:pharmacology; D000518:Eflornithine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D066298:In Vitro Techniques; D007376:Interleukin-2 / Q000096:biosynthesis*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D065108:Ornithine Decarboxylase Inhibitors; D011073:Polyamines / Q000096:biosynthesis; D011700:Putrescine / Q000494:pharmacology; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology
D007376:Interleukin-2; D065108:Ornithine Decarboxylase Inhibitors; D011073:Polyamines; D003208:Concanavalin A; D011700:Putrescine; D000518:Eflornithine