Alpha tocopherol protects against immunosuppressive and immunotoxic effects of lead

Chronic exposure to lead (Pb) is associated with multi-organ toxicity. The precise mechanism(s) involved, however, remains incompletely defined. The present study was undertaken to analyze the effect of Pb on the immune system and determine the ability of α tocopherol (AT) to reverse Pb-induced immunotoxicity. Groups of TO Mice (6 per group) were treated ip for 2 weeks with saline alone, Pb acetate alone, Pb plus AT, or with AT alone. Spleens were then analyzed for (i) cellular composition by flow cytometry, (ii) cellular response to B and T cell mitogens and (iii) production of nitric oxide (NO). Pb treatment resulted in a significant state of splenomegaly associated mainly with an influx of CD11b⁺ myeloid cells. Surprisingly, however, these cells exhibited no upregulation in expression of activation markers and did not produce NO. The lymphocyte mitogenic responses were inhibited by ≥70% in Pb-treated group. Concurrent treatment with Pb and AT resulted in almost a complete reversal of Pb-induced splenic cellular influx. Despite this, however, mitogenic responses in Pb + AT treated group were approximately 50% of those observed in normal (saline-treated) controls. We conclude that (1) chronic treatment with Pb acetate induces a state of splenomegaly and decreased proliferation in response to mitogenic stimuli and (2) co-treatment with AT largely reversed the cellular influx but this was associated with only a partial improvement of the mitogenic responses. These results highlight the role of AT as a potentially effective antioxidant in the immune system.