Cytokines as determinants of resistance and pathology in human Schistosoma mansoni infection
Cytokines as determinants of resistance and pathology in human Schistosoma mansoni infection
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DOI：
10.1590/s0100-879x1998000100024
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发表时间：
1998-01-01
影响因子：
2.3
通讯作者：
Gazzinelli, G
中科院分区：
文献类型：
--
作者：
Correa-Oliveira, R;Malaquias, LCC;Gazzinelli, G
不同细胞因子在曼氏血吸虫感染的不同临床形式和不同阶段的患者以及一组被称为正常地方性(NE)的自然抵抗感染的患者中的横断面研究中，评估了不同细胞因子在外周血单个核细胞(PBMC)增殖反应和体外肉芽肿形成中的作用。在急性(ACT)、慢性肠道(INT)和肝脾(HS)患者中，用抗IL-4和IL-5抗体阻断IL-4和IL-5显著降低了PBMC对可溶性虫卵(SEA)和成虫(SWAP)抗原的增殖反应。在体外肉芽肿形成中也得到了类似的结果。阻断IL-10对ACT和HS的PBMC检测均无显著影响，相反，在INT患者的PBMC培养中加入抗IL-10抗体显著增加了对SEA和SWAP的增殖反应以及体外肉芽肿的形成。有趣的是，抗IL-4和抗IL-10抗体的联合应用并没有增加这些患者的PBMC的增殖反应，提示IL-10可能通过调节IL-4和IL-5的分泌而起作用，当使用不同临床类型的患者的PBMC时，重组IL-10将增殖反应降低到检测不到的水平。这些数据表明，IL-10是调节曼氏血吸虫病免疫反应和控制发病率的重要细胞因子，而干扰素-γ的产生可能与抵抗感染有关。
The role of different cytokines in the peripheral blood mononuclear cell(PBMC) proliferative response and in in vitro granuloma formation was evaluated in a cross-sectional study with patients with the different clinical forms and phases of Schistosoma mansoni infection, as well as a group of individuals "naturally" resistant to infection named normal endemic (NE), The blockage of IL-4 and IL-5 using anti-IL-4 and anti-IL-5 antibodies significantly reduced the PBMC proliferative response to soluble egg (SEA) and adult worm (SWAP) antigens in acute (ACT), chronic intestinal (INT) and hepatosplenic (HS) patients, Similar results were obtained in the in vitro granuloma formation. Blockage of IL-10 had no significant effect on either assay using PBMC from ACT or HS, In contrast, the addition of anti-IL-10 antibodies to PBMC cultures from INT patients significantly increased the proliferative response to SEA and SWAP as well as the in vitro granuloma formation. Interestingly, association of anti-IL-4 and anti-IL-10 antibodies did not increase the PBMC proliferative response of these patients, suggesting that IL-10 may act by modulating IL-4 and IL-5 secretion, Addition of recombinant IL-10 decreased the proliferative response to undetectable levels when PBMC from patients with the different clinical forms were used, Analysis of IFN-gamma in the supernatants showed that PBMC from INT patients secreted low levels of IFN-gamma upon antigenic stimulation, In contrast, PBMC from NE secreted high levels of IFN-gamma. These data suggest that IL-10 is an important cytokine in regulating the immune response and possibly controlling morbidity in human schistosomiasis mansoni, and that the production of IFN-gamma may be associated with resistance to infection.