Effect of vitamin D and β-sitosterol on immune function of macrophages

Among the many functions of vitamin D (VD) is its role in the immunomodulation of macrophage. As VD deficiency is a wide-spread nutritional problem, there is a tendency for the public to overdose with vitamin D supplementation which can result in hypercalcemia and several associated disorders. The present study was designed to investigate the possibility that combining low doses of vitamin D with β-sitosterol (SIT), a common phytosterol in the diet without toxicity, enhances the efficacy of the vitamin. Murine macrophages were stimulated with LPS and supplemented with VD3 (80 nM) and SIT (8 μM) for 24 hr and examined for cell proliferation, release of nitric oxide (NO) and cytokines and the activation of NFκB. SIT (8 μM) was found to reduce cell proliferation by 62% while VD3 was found to be not effective. In combination, SIT and VD3 reduced cell proliferation by 75%.The amount of NO released, as influenced by 8 μM SIT or 80 nM VD3 treatments, was not significantly different from control. Combining SIT and VD3, resulted in a 220% greater increase in NO release compared to control. The SIT + VD3 treatment brought about significant increase in all the cytokine release, regardless of whether they were pro- or anti-inflammatory. The effects were either additive or synergistic. We conclude that SIT enhances the action of VD3 on the immune function of macrophages which could be beneficial to vitamin D deficient individuals and to those with autoimmune diseases such as multiple sclerosis.