| Summary: | 碩士 === 國立臺灣大學 === 臨床醫學研究所 === 99 === Background
The cellular and humoral immune responses in patients on chronic hemodialysis (HD) are impaired. To achieve an adequate immune response, the naïve T-cells will be differentiated to T helper cell and then to Th1 and Th2 cells after they are stimulated by pathogen. 1,25-dihydroxyvitamin D3 (1,25(OH)2D3), the activated form vitamin D is widely used in HD patients with secondary hyperparathyroidism (SHPT) and also is a well known immunomodulatory agent. Here we investigated the T cells differentiation and cytokines expression in different serum 25-hydroxyvitamin D (25(OH)D) levels patients, the T cell differentiation and cytokine results after treatment with activated vitamin D in the SHPT patients, and patient’s clinical manifestation.
Material and methods:
57 patients on chronic HD over 3 months were enrolled during January 1st, 2009 to June 30th, 2010 in Cardinal Tien Hospital and Yung-Ho Branch. Patients with systemic infection, malignancy, taking immunosuppressive medication and who took activated vitamin D or analogues in the past 3 months were all excluded. The peripheral blood mononuclear cells (PBMCs) and sera were collected while mid-week predialysis. The PBMCs were cultured and stimulated by mitogens in different time point. Then the T cells were triplely stained by surface and intracellular cytokine markers and the differentiation was analyzed by flow cytometry. The 25(OH)D level in the sera was detected by enzyme-linked immunosorbent assay (ELISA). The Th1 (interleukin (IL)-2 and interferon (IFN)-γ) and Th2 (IL-4 and IL-5) cytokine levels in the sera and culture supernatants were also evaluated by enzyme-linked immunosorbent assay (ELISA) methods.
In the SHPT patients, we prescribed the different dosage of activated vitamin D (Calcijex®, Abbott.) according to the NKF K/DOQI guideline for 3 months. Repeated previous cell culture and ELISA exam were done after 3 months later. Patient’s outcome and clinical condition would be followed and analyzed during study period.
Results
We divided the patients into 2 groups (vitamin D deficiency (VDD): <20 ng/ml in vitamin D and non-vitamin D deficiency (NVDD): ≧20 ng/ml in vitamin D) according to their 25(OH)D level. In the VDD group, the Th2 cytokine (IL-4 and IL-5) were lower in the sera, and the Th1 cytokine (IL-2 and IFN-γ) were higher and Th2 cytokine (IL-4 and IL-5) were lower in the culture supernatant. Besides, the T cell differentiation was towards to Th1 type in the VDD group, but Th2 type in the NVDD group. The T cell differentiation was not influenced by biochemistry examinations, such as albumin, hematocrit, calcium, phosphate, creatinine or dialysis vintage.
After treatment with activated vitamin D in the SHPT patients, the serum iPTH and 25(OH)D level were not significant difference. However, the level in Th1 cytokines was decreased and that of Th2 cytokines were both increased in the sera and the culture supernatant. The T cell differentiation was also more towards to Th2 phenotype than Th1 phenotype. The mortality cases were found with prevalent Th1 cell differentiation and vitamin D deficiency.
Conclusion
Our finding indicated that the T-cell differentiation is only correlated with serum 25(OH)D level. The higher vitamin D in the sera, the more prevalent in Th2 cytokines and Th2 differentiation was found. Treatment with activated vitamin D also influenced the T cell differentiation and cytokines expression in the SHPT patients. Because Th2 cell has the anti-inflammatory effect, activated vitamin D treatment may not only have therapeutic potential for secondary hyperparathyroidism, but also can improve the immune response in the chronic HD patients.
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