Oakley O R, Garvy B A, Humphreys S, Qureshi M H, Pomeroy C
Department of Clinical Sciences, University of Kentucky, Lexington, KY 40536-0084, USA.
Clin Exp Immunol. 2008 Jan;151(1):155-64. doi: 10.1111/j.1365-2249.2007.03533.x. Epub 2007 Nov 14.
The anti-inflammatory cytokine interleukin (IL)-10 plays an important role in the regulation of host-immune responses. Here we studied the role IL-10 plays in host responses to cytomegalovirus (CMV) infection. We demonstrate that manifestations of murine CMV (MCMV) disease are more severe in IL-10 knock-out mice, despite significantly reduced levels of viral replication. Cytokine analysis of serum revealed increased levels of interferon (IFN)-gamma, monocyte chemotactic protein 1 (MCP-1) and IL-6, all of which are potent stimulators of inflammatory responses. Depletion of IFN-gamma by monoclonal antibodies in IL-10 knock-out mice failed to improve the physical condition of the mice, while increasing viral replication. In contrast, serum levels of IL-6 in the knock-out animals were unaffected by IFN-gamma depletion and remained significantly elevated early in the course of infection. These data suggest that increased weight loss observed in IL-10 knock-out mice may be attributed to the uncontrolled production of proinflammatory cytokines, including IL-6.
抗炎细胞因子白细胞介素（IL）-10在宿主免疫反应调节中发挥重要作用。在此，我们研究了IL-10在宿主对巨细胞病毒（CMV）感染反应中的作用。我们证明，尽管病毒复制水平显著降低，但IL-10基因敲除小鼠的鼠巨细胞病毒（MCMV）疾病表现更为严重。血清细胞因子分析显示，干扰素（IFN）-γ、单核细胞趋化蛋白1（MCP-1）和IL-6水平升高，所有这些都是炎症反应的有效刺激物。用单克隆抗体在IL-10基因敲除小鼠中消耗IFN-γ未能改善小鼠的身体状况，同时增加了病毒复制。相反，敲除动物血清中的IL-6水平不受IFN-γ消耗的影响，并且在感染早期仍显著升高。这些数据表明，在IL-10基因敲除小鼠中观察到的体重减轻增加可能归因于包括IL-6在内的促炎细胞因子的不受控制的产生。
