Balance of pro- and anti-inflammatory cytokines correlates with outcome of acute experimental Pseudomonas aeruginosa keratitis
Balance of pro- and anti-inflammatory cytokines correlates with outcome of acute experimental Pseudomonas aeruginosa keratitis
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DOI：
10.1128/iai.70.4.2187-2197.2002
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发表时间：
2002-04-01
影响因子：
3.1
通讯作者：
Willcox, MDP
中科院分区：
文献类型：
--
作者：
Thakur, A;Xue, M;Willcox, MDP
本研究的目的是阐明感染铜绿假单胞菌的小鼠角膜中促炎和抗炎细胞因子的表达。研究人员使用了三种细菌菌株（侵入性菌株、细胞毒性菌株或 CLARE [隐形眼镜引起的急性红眼]），这些菌株最近被证明可以在小鼠中产生不同模式的角膜疾病。左小鼠（BALB/c）角膜被划伤并用三种铜绿假单胞菌菌株之一的2 x 10(6) CFU感染，而右眼作为对照。在 1、4、8、16 和 24 小时用裂隙灯生物显微镜对动物进行检查，以对感染的严重程度进行分级。检查后，收集并处理眼睛进行组织病理学、细胞因子 mRNA 的多探针 RNase 保护测定、酶联免疫吸附测定以定量细胞因子蛋白，以及髓过氧化物酶活性以定量多形核白细胞。关键细胞因子的外观动力学和表达量在铜绿假单胞菌感染的三种不同表型中存在显着差异。响应所有三种表型而表达的主要细胞因子是白细胞介素-1β (IL-1β)、IL-1Ra 和 IL-6。针对诱导严重角膜炎症的侵入性菌株，在所有时间点都存在显着较低的 IL-1Ra 与 IL-1β 比率，而用 CLARE 菌株攻击的角膜（诱导非常轻微的炎症）显示出较高的 IL-1Ra 与 IL-1β 比率。细菌性角膜炎感染的结果与这些促炎和抗炎细胞因子的相对诱导相关，外源性施用重组rIL-1Ra (rIL-1Ra)能够显着降低疾病的严重程度。这些发现表明 rIL-1Ra 蛋白在细菌性角膜炎的可能治疗策略中具有治疗潜力。
The purpose of this study was to elucidate the expression of pro- and anti-inflammatory cytokines in mouse corneas infected with Pseudomonas aeruginosa. Three bacterial strains (invasive, cytotoxic, or CLARE [contact lens-induced acute red eye]) which have recently been shown to produce distinct patterns of corneal disease in the mouse were used. The left mouse (BALB/c) corneas were scarified and infected with 2 x 10(6) CFU of one of the three P. aeruginosa strains, while right eyes served as controls. Animals were examined at 1, 4, 8, 16, and 24 h with a slit lamp biomicroscope to grade the severity of infection. Following examination, eyes were collected and processed for histopathology, multiprobe RNase protection assay for cytokine mRNA, enzyme-linked immunosorbent assay to quantitate cytokine proteins, and myeloperoxidase activity to quantitate polymorphonuclear leukocytes. The kinetics of appearance and magnitude of expression of key cytokines varied significantly in the three different phenotypes of P. aeruginosa infection. The predominant cytokines expressed in response to all three phenotypes were interleukin-1beta (IL-1beta), IL-1Ra, and IL-6. In response to the invasive strain, which induced severe corneal inflammation, significantly lower ratios of IL-1Ra to IL-1beta were present at all time points, whereas corneas challenged with the CLARE strain, which induced very mild inflammation, showed a high ratio of IL-1Ra to IL-1beta. The outcome of infection in bacterial keratitis correlated with the relative induction of these pro- and anti-inflammatory cytokines, and exogenous administration of recombinant rIL-1Ra (rIL-1Ra) was able to reduce the disease severity significantly. These findings point to the therapeutic potential of rIL-1Ra protein in possible treatment strategies for bacterial keratitis.