Karp C L, el-Safi S H, Wynn T A, Satti M M, Kordofani A M, Hashim F A, Hag-Ali M, Neva F A, Nutman T B, Sacks D L
Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland 20892.
J Clin Invest. 1993 Apr;91(4):1644-8. doi: 10.1172/JCI116372.
The immunological mechanisms underlying the susceptibility to disseminated visceral parasitism of mononuclear phagocytes in patients with kala-azar remain undefined. Resistance and susceptibility are correlated with distinct patterns of cytokine production in murine models of disseminated leishmanial disease. To assess lesional cytokine profiles in patients with kala-azar, bone marrow aspirates were analyzed using a quantitative reverse transcriptase PCR technique to amplify specific mRNA sequences of multiple Th1-, Th2-, and/or macrophage-associated cytokines. Transcript levels of IL-10 as well as IFN-gamma were significantly elevated in patients with active visceral leishmaniasis; IL-10 levels decreased markedly with resolution of disease. These findings suggest that IL-10, a potent, pleiotropic suppressor of all known microbicidal effector functions of macrophages, may contribute to the pathogenesis of kala-azar by inhibiting the cytokine-mediated activation of host macrophages that is necessary for the control of leishmanial infection.
黑热病患者单核吞噬细胞易发生播散性内脏寄生的免疫机制仍不明确。在播散性利什曼病的小鼠模型中，抵抗力和易感性与细胞因子产生的不同模式相关。为了评估黑热病患者病变部位的细胞因子谱，采用定量逆转录聚合酶链反应技术分析骨髓穿刺物，以扩增多种Th1、Th2和/或巨噬细胞相关细胞因子的特异性mRNA序列。活动性内脏利什曼病患者的IL-10以及IFN-γ转录水平显著升高；随着疾病的缓解，IL-10水平明显下降。这些发现表明，IL-10是巨噬细胞所有已知杀菌效应功能的一种强大的、多效性抑制剂，它可能通过抑制细胞因子介导的宿主巨噬细胞激活而促进黑热病的发病机制，而这种激活对于控制利什曼原虫感染是必需的。
