Inhibitory effect of vitamin E on proinflammatory cytokines-and endotoxin-induced nitric oxide release in alveolar macrophages

Nitric oxide is thought to be an important modulator of various functions in normal and inflamed airways. In the present study, we evaluated the effects of high vitamin E (250 mg and 1250 mg α-tocopheryl acetate (TA)/kg diet/10 days) on nitric oxide (NO) release by alveolar macrophages (AMs) in response to lipopolysaccharide (LPS), interleukin-1β (IL-1β) and tumor necrosis factor (TNF-α). LPS and IL-1β treatment (1-10 μg/ml) enhanced NO release in AMs from control animals fed on 50 mg vitamin E/kg diet in a concentration dependent manner. However, this enhancement of NO was attenuated in the AMs of animals fed with 250 mg or 1250 mg vitamin E/kg diet. TNF-α had no effect in eliciting the release of NO in AMs obtained either from control or from hyper vitamin E fed animals. Further, LPS (1-10 μg/ml) enhanced the inducible nitric oxide synthase (iNOS) activity of AMs of control group and TA-fed animals almost to equal extent. Similarly, LPS-induced formation of N-nitrosamine (N-nitroso-L-[14C]-proline) in AMs of control and TA-supplemented animals were not different statistically. On the other hand, in vitro addition of vitamin E (200 μM) in AMs of control animals, when triggered with 10 μg LPS/ml, caused a significant decrease in N-nitroso-L-[14C]-proline formation. It seems that high doses of TA in diet may play a role in reducing the lipopolysaccharide and proinflammatory cytokines-induced NO-mediated damage by AMs.