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猪蛔虫提取物在自身免疫性肝炎实验模型中对肝损伤的免疫调节作用

Immunomodulation of liver injury by Ascaris suum extract in an experimental model of autoimmune hepatitis.

作者信息

Nascimento Wheverton C, Silva Roeckson P, Fernandes Erica S, Silva Maria C, Holanda Gabriela C, Santos Patrícia A, Albuquerque Mônica P, Costa Vlaudia A, Pontes-Filho Nicodemos T, Souza Valdênia O

机构信息

Laboratory of Immunopathology Keizo Asami, Federal University of Pernambuco, 50.670-901, Pernambuco, Brazil.

出版信息

Parasitol Res. 2014 Sep;113(9):3309-17. doi: 10.1007/s00436-014-3994-6. Epub 2014 Jun 21.

Abstract

Adult worm extract from Ascaris suum (Asc) has immunosuppressive activity and elicits Th2/IL-4/IL-10 response. This study evaluated the prophylactic and therapeutic effect of Asc in a murine model of concanavalin A (ConA)-induced autoimmune hepatitis (AIH). BALB/c mice received ConA, iv, (20 mg/kg), and three groups of animals were formed: (1) AIH, received only ConA; (2) AIH + Asc prophylactic, treated with Asc (1 mg/ml), ip, 30 min before of the AIH; and (3) AIH + Asc therapeutic, treated with Asc 2 h after the AIH. Plasma transaminase and immunoglobulins (measured at 8 and 24 h and 7 days after treatment) and cytokine production (IL-4, IL-10, IL-13, and IFN-γ) by splenocytes upon ConA and Asc stimulus were compared. The livers were weighed and examined histologically. In the AIH group, there was an increase in liver weight, transaminase levels, and total immunoglobulins. These parameters were reduced by 8-24 h and 7 days in the prophylactic group, but in the therapeutic group, only on day 7. The survival rate of mice in the AIH group was 38.5%, compared to 67% in the therapeutic Asc group. The survival rate of the animals with AIH that were prophylactically treated with Asc was 100%. A decrease of cellular infiltration and high levels of IL-4, IL-10, and IL-13 were induced by Asc. An increase of liver fibrosis was also observed, but with less intensity with prophylactic treatment. Thus, the Ascaris components have an inhibitory effect on AIH, with an intense Th2 immune response.

摘要

猪蛔虫成虫提取物(Asc)具有免疫抑制活性,并引发Th2/IL-4/IL-10反应。本研究评估了Asc在刀豆蛋白A(ConA)诱导的自身免疫性肝炎(AIH)小鼠模型中的预防和治疗作用。BALB/c小鼠静脉注射ConA(20 mg/kg),并分为三组动物:(1)AIH组,仅接受ConA;(2)AIH+Asc预防组,在AIH前30分钟腹腔注射Asc(1 mg/ml);(3)AIH+Asc治疗组,在AIH后2小时给予Asc治疗。比较了治疗后8小时、24小时和7天的血浆转氨酶和免疫球蛋白,以及ConA和Asc刺激后脾细胞产生的细胞因子(IL-4、IL-10、IL-13和IFN-γ)。称量肝脏重量并进行组织学检查。在AIH组中,肝脏重量、转氨酶水平和总免疫球蛋白增加。这些参数在预防组中在8-24小时和7天时降低,但在治疗组中仅在第7天降低。AIH组小鼠的存活率为38.5%,而治疗性Asc组为67%。Asc预防性治疗的AIH动物的存活率为100%。Asc诱导细胞浸润减少以及IL-4、IL-10和IL-13水平升高。还观察到肝纤维化增加,但预防治疗时程度较轻。因此,蛔虫成分对AIH具有抑制作用,并伴有强烈的Th2免疫反应。

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