الفهرس 
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Abstract
Asthma is a chronic lung disease characterized by airway hyperresponsiveness, airway inflammation, and mucous hypersecretion. The reported incidence rate of asthma has been increasing both in the industrialized and developing countries over the last four decades.
It is established that allergic asthma is characterized by a Th-2 dominant inflammatory immune response. The Th-2 cell cytokine IL-4 was found to be associated with disease severity. The ability of the airways epithelium and several immune system cells to synthesis the active form of vitamin D, 1,25(OH)2D3, besides the expression of VDR in several immune system cells postulate a paracrine/autocrine role for 1,25(OH)2D3 in lung tissue and immune cells.
The aim of this study was to evaluate possible in vitro immunomodulatory effects of 1,25(OH)2D3 on the production of IL-4 by activated T lymphocytes in allergic asthmatics.
The current study was conducted on 30 randomly chosen adults: 20 mild atopic asthmatics and 10 age and sex matched normal healthy control subjects. All asthmatic patients were sensitive to DP and/or DF HDM allergens as estimated by skin prick test. Specific co-stimulatory T cell activation in cultured PBMCs was induced by immobilized anti-CD3 plus soluble anti-CD28 mAbs. The effect of 1,25(OH)2D3 on the production of IL-4 by activated T cells was assessed in culture supernatant by ELISA.
In absence of T cell activation, no detectable levels of IL-4 were found in PBMCs culture supernatant of both mild atopic asthmatics and healthy subjects. After T cell activation, PBMCs culture supernatants of mild atopic asthmatics showed a significant increased production of IL-4 compared to PBMCs cultures of healthy subjects. This finding addresses the Th-2 skewing in atopic asthmatics, and highlights the possibility that targeting IL-4 and/or its receptor may provide some clinical benefits in this class of asthmatic patients.
Compared to ethanol as vehicle control, current results showed that 1,25(OH)2D3, particularly at the concentration of 10-6 mol/L, significantly increases in vitro IL-4 production by activated T cells both in healthy subjects and mild atopic asthmatic patients. These results suggest 1,25(OH)2D3 as a risk factor for developing asthma and increase in asthma severity.
Vitamin D supplementation is generally recommended for asthmatic patients who need long-term inhaled or oral glucocorticoids therapy to minimize glucocorticoid-induced osteoporosis. Current data suggest that active form of vitD, 1,25(OH)2D3, may blunt the desired inhibitory effect of glucocorticoids on Th-2 cell-mediated allergic airway inflammation by elevating the level of IL-4 produced by activated T cells particularly in mild atopic asthmatics.
In conclusion, active form of vitamin D, 1,25(OH)2D3, increases the level of IL-4 produced by activated T cells in both of allergic asthmatics and healthy control subjects. Therefore, its high levels may have a negative influence on allergic asthma incidence and severity. This study should be taken in consideration by health care professionals before prescribing vitamin D supplements for patients with allergic asthma or individuals at high risk of developing this disease.