Effects of vitamin D3 and vitamin E on prednisolone-induced alterations of phagocyte function.

OBJECTIVE: To evaluate the effectiveness of vitamin D3 and its combined action with vitamin E in the correction of the impairments of phagocyte function caused by chronic glucocorticoid administration. MATERIALS AND METHODS: Phagocytic activity was assessed by the ability of peripheral blood neutrophils and monocytes to capture FITC-labeled Escherichia coli using flow cytometry. Metabolic activity of neutrophils was measured cytochemically as nitro blue tetrazolium (NBT) reduction test. Intracellular reactive oxygen species (ROS) were detected by 2',7'-dichlorofluorescein fluorescence. RESULTS: Prednisolone administration (5 mg/kg b.w., 30 days) was accompanied by vitamin D3 deficiency and decompensation of phagocyte function associated with antimicrobial activity (decrease in NBT reduction rate, ROS formation and phagocytic activity). Vitamin D3 co-administration with prednisolone and, to a greater extent, its combination with α-tocopherol (100 IU and 0.5 mg/rat, 30 days respectively) partially restored phagocyte function. CONCLUSIONS: These data suggest that vitamin D3 and α-tocopherol can prevent immunosuppressive effects of prednisolone through elevating the efficacy of oxygen-dependent mechanisms of phagocytosis and increasing the functional activity of phagocytic cells.

Prednisolone and vitamin D(3) modulate oxidative metabolism and cell death pathways in blood and bone marrow mononuclear cells.

The study was designed to evaluate reactive oxygen species (ROS)/nitric oxide (NO) formation and apoptotic/necrotic cell death elicited by prednisolone in peripheral blood and bone marrow mononuclear cells and to define the efficacy of vitamin D3 to counter glucocorticoid (GC)-induced changes. It was shown that prednisolone (5 mg per kg of female Wistar rat's body weight for 30 days) evoked ROS and NO overproduction by blood mononuclear cells (monocytes and lymphocytes) that correlated with increased cell apoptosis and necrosis. In contrast, prednisolone did not affect ROS/NO levels in bone marrow mononuclear cells that corresponded to lower level of cell death than in the control. Alterations of prooxidant processes revealed in mononuclear cells and associated with GC action were accompanied by vitamin D3 deficiency in animals, which was assessed by the decreased level of blood serum 25-hydroxivitamin D3 (25OHD3). Vitamin D3 administration (100 IU per rat daily for 30 days, concurrently with prednisolone administration) completely restored 25OHD3 content to the control values and significantly reversed ROS and NO formation in blood mononuclear cells, thus leading to decreased apoptosis. In bone marrow, vitamin D3 activated ROS/NO production and protein nitration that may play a role in prevention of prednisolone-elicited increase in bone resorption. We conclude that vitamin D3 shows a profound protection against GC-associated cellular damage through regulating intracellular ROS/NO formation and cell death pathways.