阿仑膦酸钠维D3或维生素D2预处理对首次静脉输注唑来膦酸炎症细胞因子及外周血T淋巴细胞的影响

Effects of pretreatment with alendronate sodium with vitamin D3 or vitamin D2 on inflammatory cytokines and peripheral blood T lymphocytes after the first intravenous infusion of zoledronic acid

目的研究阿仑膦酸钠维D3、单次肌肉注射维生素D2预处理对首次静脉输注唑来膦酸治疗绝经后骨质疏松症患者外周血炎症细胞因子及T淋巴细胞亚群的影响。方法选取绝经后骨质疏松症患者97例,按照随机数字表法随机分为口服阿仑膦酸钠维D3预处理组(阿仑膦酸钠维D3组,n=33)、单次肌肉注射维生素D2组(维生素D2组,n=31)、无预处理组(对照组,n=33)。首次静脉输注唑来膦酸前及输注唑来膦酸24 h后留取外周血,比较分析3组的临床资料、输注唑来膦酸前后外周血炎症细胞因子、T淋巴细胞表面标志物。结果对照组、维生素D2组、阿仑膦酸钠维D3组输注唑来膦酸前外周血炎症细胞因子白细胞介素-6(interleukin-6,IL-6)、肿瘤坏死因子α(tumor necrosis factor-α,TNF-α)、γ干扰素(interferon-γ,IFN-γ)及T淋巴细胞表面标志物CD3^(+)、CD3^(+)/CD3^(+)CD69^(+)(CD3^(+)与CD3^(+)CD69^(+)两者比值)差异均无统计学意义(均P>0.05)。三组静脉输注唑来膦酸后IL-6、TNF-α、IFN-γ均较输注前升高(均P<0.05),对照组静脉输注唑来膦酸后IL-6升高水平高于其他两组(P<0.05),维生素D2组高于阿仑膦酸钠维D3组(P=0.002)。三组静脉输注唑来膦酸后TNF-α、IFN-γ升高水平差异均无统计学意义。三组静脉输注唑来膦酸后CD3^(+)T淋巴细胞均较输注前减少,阿仑膦酸钠维D3组CD3^(+)T淋巴细胞减少程度低于对照组(P=0.040)。三组静脉输注唑来膦酸后CD3^(+)/CD3^(+)CD69^(+)T淋巴细胞均较前增多,且对照组、维生素D2组较阿仑膦酸钠维D3组增加更多(P=0.047、0.046)。三组静脉输注唑来膦酸前后CD3^(+)/CD3^(+)TCRγδ^(+)、CD3^(+)/CD3^(+)TCRγδ^(+)/CD27-IL-23R^(+)、CD3^(+)/CD3^(+)TCRγδ^(+)/CD27-IL-23R-、CD3^(+)/CD3^(+)TCRγδ^(+)/CD27^(dim) IL-23R-、CD3^(+)/CD3^(+)TCRγδ^(+)/CD27 High IL-23R-水平差值差异均无统计学意义。结论阿仑膦酸钠维D3、维生素D2预处理可减少首次静脉输注唑来膦酸引起急性时相反应的相关炎症细胞因子IL-6的产生,阿仑膦酸钠维D3预处理保留了静脉输注唑来膦酸后的CD3^(+)T淋巴细胞数目,减少CD3^(+)/CD3^(+)CD69^(+)T淋巴细胞的产生,减少炎症相关淋巴细胞活化,可减轻首次静脉输注唑来膦酸出现的急性时相反应。

Objective To investigate the effects of pretreatment with alendronate sodium with vitamin D3 or a single intramuscular injection of vitamin D2 on peripheral blood inflammatory cytokines and T lymphocyte subsets in postmenopausal women with osteoporosis who received the first infusion of zoledronic acid.Methods A total of 97 postmenopausal women with osteoporosis were randomly divided into three groups as alendronate sodium with vitamin D3 group(n=33),vitamin D2 group(n=31),and control group(n=33)by a random number table.Peripheral blood was collected before and 24 hours after the first infusion of zoledronic acid.The clinical data,peripheral blood inflammatory cytokines and T lymphocyte surface markers before and after infusion of zoledronic acid were compared and analyzed among the three groups.Results There were no statistically significant differences in inflammatory cytokines like interleukin-6(IL-6),tumor necrosis factor-α(TNF-α)and interferon-γ(IFN-γ)and peripheral blood T lymphocyte surface markers like CD3^(+)and CD3^(+)/CD3^(+)CD69^(+)among the three groups before intravenous infusion of zoledronic acid(all P>005).IL-6,TNF-αand INF-γwere significantly higher after infusion of zoledronic acid than baseline in all the three groups(all P<0.05).The increase of IL-6 was significantly higher in the control group than in the other two groups(P<0.05),and was higher in the vitamin D2 group than in the alendronate sodium with vitamin D3 group(P=0.002).There were no significant differences in the increase of TNF-αand INF-γafter infusion of zoledronic acid among the three groups.CD3^(+)T lymphocytes decreased in all groups after the infusion,with the alendronate sodium with vitamin D3 group showing a lesser reduction than the control group(P=0.040).The proportion of CD3^(+)/CD3^(+)CD69^(+)T lymphocytes increased in all groups after the infusion,with a more significant increase in the control and vitamin D2 groups compared to the alendronate sodium with vitamin D3 group(P=0.047,P=0.046).There were no significant differences in the changes of CD3^(+)/CD3^(+)TCRγδ^(+),CD3^(+)/CD3^(+)TCRγδ^(+)/CD27-IL-23R^(+),CD3^(+)/CD3^(+)TCRγδ^(+)/CD27-IL-23R-,CD3^(+)/CD3^(+)TCRγδ^(+)/CD27^(dim) IL-23R-,and CD3^(+)/CD3^(+)TCRγδ^(+)/CD27 High IL-23R-levels before and after the infusion among the three groups.Conclusion Pretreatment with alendronate sodium with vitamin D3 or vitamin D2 can reduce IL-6 production associated with the acute-phase response induced by the first intravenous infusion of zoledronic acid.Pretreatment with alendronate sodium with vitamin D3 preserves the number of CD3^(+)T lymphocytes,decreases the production of CD3^(+)/CD3^(+)CD69^(+)T lymphocytes,reduces the activation of inflammatory related lymphocytes,and alleviates the acute-phase response during the first infusion of zoledronic acid.