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胸腺肽α1与大剂量地塞米松联合治疗慢性特发性血小板减少性紫癜患者

[Combination therapy of thymosin alpha1 and high dose dexamethasone in patients with chronic idiopathic thrombocytopenic purpura].

作者信息

Wang Lin, Guo Cheng-shan, Hou Ming, Li Li-zhen, Zhang Chun-qing, Chen Feng, Qin Ping, Peng Jun, He Wei-dong, Chu Xiao-xia

机构信息

Department of Hematology, Qilu Hospital, Shandong University, Jinan 250012, China.

出版信息

Zhonghua Nei Ke Za Zhi. 2007 Apr;46(4):274-6.

PMID:17637261
Abstract

OBJECTIVE

To study the efficacy and mechanism of thymosin alpha(1) (Talpha(1)) combined with high dose dexamethasone (HD-Dex) in patients with chronic idiopathic thrombocytopenic purpura.

METHODS

(1) Out of sixty-six newly diagnosed patients with chronic idiopathic thrombocytopenic purpura, 27 patients received oral HD-Dex at single daily doses of 40 mg for 4 consecutive days, 39 patients received HD-Dex plus Talpha(1) 1.6 mg subcutaneously thrice weekly for 4 weeks. (2) The plasma levels of Talpha(1), IFNgamma, IL-2, IL-4, IL-10 and TGF-beta(1) of the 66 patients and 20 healthy controls were detected with ELISA.

RESULTS

(1) Twelve patients (44.4%) in HD-Dex treatment group and thirty patients (76.9%) in HD-Dex plus Talpha(1) treatment group achieved complete response respectively (P < 0.05). After a follow-up period of 6 months, HD-Dex plus Talpha(1) treatment group showed a significantly greater rate of sustained response (24/39, 61.5%) and a lower replacing rate (15/39, 38.5%) than HD-Dex treatment group (9/26, 34.6%; 17/26, 65.4%) (P < 0.05). (2) After treatment, a remarkable decrease of Talpha(1) levels was seen HD-Dex plus Talpha(1) treatment group [(2.43 +/- 1.47), (1.83 +/- 1.22)] microg/L (P < 0.05). (3) In HD-Dex plus Talpha(1) treatment group, the plasma levels of both IFNgamma and IL-2 were significantly higher [(22.71 +/- 7.98), (28.42 +/- 11.27)] ng/L than those in controls [(10.23 +/- 3.97), (8.73 +/- 8.22)] ng/L (P < 0.01). The levels of both IL-4 and IL-10 were significantly lower [(5.93 +/- 3.85), (3.24 +/- 1.36)] ng/L after treatment as compared with those in the controls [(14.39 +/- 8.03), (8.67 +/- 3.04)] ng/L (P < 0.01). After treatment, IFNgamma and IL-2 decreased [(11.57 +/- 4.33), (14.56 +/- 10.76)] ng/L (P < 0.01) and IL-4 and IL-10 increased greatly [(9.87 +/- 4.82), (7.90 +/- 2.71)] ng/L (P < 0.05). (4) TGF-beta(1) in HD-Dex plus Talpha(1) treatment group significantly increased from [(1.31 +/- 0.71), (4.19 +/- 1.80)] microg/L after treatment (P < 0.01). (5) There was a significantly positive correlation between Talpha(1) and TGF-beta(1) (r = 0.6028, P < 0.05).

CONCLUSIONS

(1) Combination therapy of Talpha(1) and HD-Dex seems to be effective and safe in newly diagnosed patients with ITP. (2) Talpha(1) may balance the Th1/Th2/Th3 subgroups and induce a physiologic immunosuppressive effect of NK cells and autoimmune tolerance.

摘要

目的

研究胸腺素α1(Tα1)联合大剂量地塞米松(HD-Dex)治疗慢性特发性血小板减少性紫癜患者的疗效及机制。

方法

(1)66例新诊断的慢性特发性血小板减少性紫癜患者中,27例患者连续4天每日口服40mg HD-Dex,39例患者接受HD-Dex联合Tα1皮下注射,每周3次,每次1.6mg,共4周。(2)采用酶联免疫吸附测定法(ELISA)检测66例患者及20例健康对照者血浆中Tα1、干扰素γ(IFNγ)、白细胞介素-2(IL-2)、白细胞介素-4(IL-4)、白细胞介素-10(IL-10)和转化生长因子-β1(TGF-β1)水平。

结果

(1)HD-Dex治疗组12例患者(44.4%)和HD-Dex联合Tα1治疗组30例患者(76.9%)分别达到完全缓解(P<0.05)。随访6个月后,HD-Dex联合Tα1治疗组持续缓解率显著高于HD-Dex治疗组(24/39,61.5%比9/26,34.6%),复发率低于HD-Dex治疗组(15/39,38.5%比17/26,65.4%)(P<0.05)。(2)治疗后,HD-Dex联合Tα1治疗组Tα1水平显著降低[(2.43±1.47),(1.83±1.22)]μg/L(P<0.05)。(3)HD-Dex联合Tα1治疗组血浆IFNγ和IL-2水平显著高于健康对照组[(22.71±7.98),(28.42±11.27)]ng/L比[(10.23±3.97),(8.73±8.22)]ng/L(P<0.01)。治疗后IL-4和IL-10水平显著低于健康对照组[(5.93±3.85),(3.24±1.36)]ng/L比[(14.39±8.03),(8.67±3.04)]ng/L(P<0.01)。治疗后,IFNγ和IL-2降低[(11.57±4.33),(14.56±l0.76)]ng/L(P<0.01),IL-4和IL-10显著升高[(9.87±4.82),(7.90±2.71)]ng/L(P<0.05)。(4)HD-Dex联合Tα1治疗组TGF-β1水平治疗后显著升高,由[(1.31±0.71),(4.19±1.80)]μg/L(P<0.01)。(5)Tα1与TGF-β1呈显著正相关(r=0.6028,P<0.05)。

结论

(1)Tα1联合HD-Dex治疗新诊断的ITP患者似乎有效且安全。(2)Tα1可能平衡Th1/Th2/Th3亚群,诱导NK细胞产生生理性免疫抑制作用及自身免疫耐受。

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