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The role of macrophages (M phi) in the enhancement of lymphocyte proliferation by alpha-tocopherol (VE) was investigated using rat splenocytes. The proliferation of whole splenocytes was significantly higher than that of M phi-depleted splenocytes at all concentrations of concanavalin A (Con A; 0.5-10 micrograms/ml). When whole and M phi-depleted splenocytes were preincubated with VE (2 micrograms/ml) for 24 h, the proliferation of whole splenocytes was significantly enhanced compared to that of whole splenocytes preincubated with medium alone. In contrast, M phi-depleted splenocytes did not show any increase of proliferation following in vitro pretreatment with VE. When the splenic: M phi pretreated with both VE (2 micrograms/ml) and Con A (10 micrograms/ml) for 24 h were further incubated with splenic lymphocytes, their proliferation was significantly enhanced compared to that of splenic lymphocytes cultured with splenic M phi pretreated with Con A. In this experiment, the medium containing 2-mercaptoethanol (2-ME) had the ability to enhance splenic lymphocyte proliferation, which masked the enhanced effect of VE on splenic: lymphocyte proliferation. Furthermore, in vitro treatment of VE could not decrease the production of prostaglandin E2, but could enhance the production of interleukin 1 from splenic M phi. These results suggest that M phi play an important role in the proliferation of splenic lymphocytes following in vitro incubation with VE, which is closely associated with the action of VE as an immunomodulator rather than antioxidant.

The Role of Macrophages in Increased Mitogen Response of Rat Splenic Lymphocytes Following in Vitro Incubation with Vitamin E.