Murray Henry W, Moreira Andre L, Lu Cristina M, DeVecchio Jennifer L, Matsuhashi Maki, Ma Xiaojing, Heinzel Frederick P
Department of Medicine, Weill Medical College of Cornell University, New York, USA.
J Infect Dis. 2003 Aug 1;188(3):458-64. doi: 10.1086/376510. Epub 2003 Jul 14.
In established Leishmania donovani visceral infection in normal mice, anti-interleukin (IL)-10 receptor (IL-10R) monoclonal antibody (MAb) treatment induced intracellular parasite killing within liver macrophages. IL-10R blockade maintained IL-12 protein 40, markedly increased interferon (IFN)-gamma serum levels, and enhanced tissue inducible nitric oxide synthase (iNOS) expression and granuloma assembly. Optimal MAb-induced killing, including synergism with antimony chemotherapy, required endogenous IL-12 and/or IFN-gamma and at least one IFN-gamma-regulated macrophage mechanism-iNOS or phagocyte oxidase. However, in IFN-gamma knockout mice, anti-IL-10R also induced both granuloma formation and leishmanistatic activity. As judged by IL-10R blockade, endogenous IL-10 primarily regulates killing in L. donovani infection by suppressing production of and responses to the Th1 cell-type cytokines, IL-12, and IFN-gamma. However, because anti-IL-10R also released IFN-gamma-independent effects, IL-10 appears to act more broadly and suppresses multiple antileishmanial mechanisms.
在正常小鼠已建立的杜氏利什曼原虫内脏感染模型中，抗白细胞介素（IL）-10受体（IL-10R）单克隆抗体（MAb）治疗可诱导肝巨噬细胞内的寄生虫被杀伤。阻断IL-10R可维持IL-12蛋白水平，显著提高干扰素（IFN）-γ血清水平，并增强组织诱导型一氧化氮合酶（iNOS）表达和肉芽肿形成。单克隆抗体诱导的最佳杀伤效果，包括与锑化疗的协同作用，需要内源性IL-12和/或IFN-γ以及至少一种IFN-γ调节的巨噬细胞机制——iNOS或吞噬细胞氧化酶。然而，在IFN-γ基因敲除小鼠中，抗IL-10R也可诱导肉芽肿形成和利什曼原虫抑制活性。通过阻断IL-10R判断，内源性IL-10主要通过抑制Th1细胞型细胞因子IL-12和IFN-γ的产生及反应来调节杜氏利什曼原虫感染中的杀伤作用。然而，由于抗IL-10R也释放出不依赖IFN-γ的效应，IL-10似乎具有更广泛的作用，并抑制多种抗利什曼原虫机制。
Zotero 插件