甲泼尼龙治疗对慢性乙型肝炎重症化趋势患者外周血树突细胞的影响与临床意义

Effect of methylprednisolone on peripheral blood dendritic cells in patients with exacerbation of chronic hepatitis B and clinical significance

目的：探讨甲泼尼龙对呈重症化趋势慢性乙型肝炎（CHB）患者外周血树突细胞（DCs）的影响与临床意义。方法纳入2012年12月至2015年6月收治住院的有进展为慢加急性乙型肝炎肝衰竭趋势患者51例，随机分为甲泼尼龙组25例，对照组26例。对照组采用常规综合治疗，甲泼尼龙组在常规治疗基础上加用甲泼尼龙降阶梯治疗7 d 后停用。用流式细胞仪对两组患者外周血髓系树突细胞（mDCs）和浆细胞样树突细胞（pDCs）进行计数，通过酶联免疫吸附试验检测白介素（IL）-12、干扰素（IFN）α水平以评价 mDCs 和 pDCs 的功能。采用配对或成组 t 检验比较两组患者DCs 计数与功能变化，采用 Kaplan-Meier 法分析两组的累计生存率。结果甲泼尼龙组 mDCs 计数在治疗第3、第7天低于对照组（t ＝4．029和2．558，P 〈0．05和〈0．01），pDCs 计数在第3、第10天均低于对照组（t ＝3．870和3．330，P 值均〈0．01）；停用甲泼尼龙后，mDCs 和 pDCs 计数上升，与对照组相比差异无统计学意义（P 〉0．05）。甲泼尼龙治疗组 IL-12水平在第3、第7和第10天均低于对照组（t ＝3．787、4．841和2．833，P 值均〈0．01），IFNα在第3、第7、第10和第14天均低于对照组（t ＝2．786、6．005、2．814和3．557，P 值均〈0．01）；停用甲泼尼龙后，IL-12和 IFNα水平上升，与对照组相比差异无统计学意义（P 〉0．05）。甲泼尼龙组3个月累计生存率高于对照组（χ^2＝5．684，P 〈0．05）。甲泼尼龙组中，21例存活者 DCs 计数停用甲泼尼龙后上升，而4例死亡者 DCs 计数在停用甲泼尼龙后仍持续低于治疗前水平。结论甲泼尼龙通过抑制 DCs 减轻了 CHB 重症化过强的免疫应答，这可能是激素阻抑重症化 CHB 患者发生肝衰竭、改善预后的免疫学机制之一。

Objective To investigate the effect and clinical significance of methylprednisolone on dendritic cells （DCs）in patients with exacerbation of chronic hepatitis B（CHB）.Methods Fifty one patients with exacerbation of CHB admitted during December 201 2 and June 201 5 were randomly divided into methylprednisolone group （25 patients）and control group （26 patients）.Patients in both groups were treated with antiviral,hepatoprotective and symptomatic therapy,patients in methylprednisolone group received additional methylprednisolone therapy by deescalation for 7 days.Flow cytometry was used to detect the myloid dendritic cells （mDCs）and plasmacytoid dendritic cells （pDCs）in two groups.Serum IL-1 2 and IFNαlevels were detected with enzyme linked immunosorbent assay for evaluation of the function of mDCs and pDCs.Pair t test and group t test were used to analyze the counts and function of mDCs and pDCs, Kaplan-Meier method was used to analyze the cumulative survival rate.Results In methylprednisolone＆amp;nbsp;group,the mDCs counts were lower than those in control group at d3 and d7 （t =4.029 and 2.558,P 〈0.01 and 〈0.05）,and the pDCs counts were lower than those in control group at d3 and d1 0 （t =3.870 and 3.330,all P 〈0.01 ）.After the withdrawal of methylprednisolone,mDCs and pDCs counts were successively rebound to the similar levels of the control group （P 〉0.05 ）.The levels of IL-1 2 in methylprednisolone group were lower than those in control group at d3,d7 and d1 0 （t =3.787,4.841 and 2.833,all P 〈0.01 ）,and the levels of IFNαwere lower than those in control group at d3,d7,d1 0 and d1 4 （t =2.786,6.005,2.81 4 and 3.557,all P 〈0.01 ）.After the withdrawal of methylprednisolone, IL-1 2 and IFNαlevels were successively rebound to the similar levels of the control group （P 〉0.05）.The cumulative survival rate of methylprednisolone group was higher than that of the control group （χ^2 =5.684, P 〈0.05）.In the methylprednisolone group,the counts of DCs in twenty-one survivors began to increase to the levels of before treatment after the withdrawal of methylprednisolone;while the counts of DCs in 4 fatal cases did not return to the levels of before treatment.Conclusions Methylprednisolone can attenuate the super intensive immune response by inhibiting DCs in patients with exacerbation of CHB,which may protect patients from liver failure and improve the prognosis.