Proinflammatory cytokine deficiency and pathogenesis of Pseudomonas aeruginosa keratitis in aged mice
Proinflammatory cytokine deficiency and pathogenesis of Pseudomonas aeruginosa keratitis in aged mice
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DOI：
10.1128/iai.65.7.2754-2758.1997
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发表时间：
1997-07-01
影响因子：
3.1
通讯作者：
Hazlett, LD
中科院分区：
文献类型：
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作者：
Hobden, JA;Masinick, SA;Hazlett, LD
绿脓杆菌感染后，年轻成年瑞士（HSD：ICR）小鼠的角膜透明度恢复。以前的数据表明，这种反应涉及组成性细胞间粘附分子-1（ICAM-1）的快速上调和炎性细胞向角膜中的迁移。相反，在老年小鼠中，角膜ICAM-1没有上调，炎性细胞浸润到角膜中被延迟，并且角膜穿孔。因此，本研究的目的是测试是否特定的细胞因子，上调ICAM-1的表达不同，在年轻和老年小鼠。将年轻（6- 8周龄）和老年（1- 2岁）小鼠的角膜划痕并接种铜绿假单胞菌。对眼睛的病理变化进行分级（评分0至+4）;在感染后6、12、24和48小时（p.i.），每个年龄组处死6只螨。从每组中切下三个角膜，通过酶联免疫吸附测定法定量白细胞介素-1 β（IL-1 β）、肿瘤坏死因子α和γ干扰素（IFN-γ）。从每个年龄组中收获剩余的三个角膜，通过干平板计数测定活细菌的数量，并通过髓过氧化物酶（MPO）测定浸润的多形核白细胞（PMN）。感染后6 h，老年小鼠角膜IL-1 β含量较青年小鼠低。（P小于或等于0.04），并且在12至48 h p.i.（P <0.05）。此外，与年轻小鼠相比，老年小鼠角膜在接种后6 h的MPO测定中具有较少的PMN（P小于或等于0.008）。在感染后23 h，通过平板计数测定，每个角膜的活菌数更多（P小于或等于0.01）。这些数据表明，老年人眼ICAM-1上调的缺乏可能反映了感染角膜中IL-1 β和IFN-γ水平的降低。因此，足够数量的中性粒细胞和其他炎症细胞不能迅速迁移到老年小鼠的感染角膜中，细菌负荷最初大于年轻小鼠中的细菌负荷，并且角膜穿孔。
Corneal clarity in young adult Swiss (HSD:ICR) mice is restored after Pseudomonas aeruginosa infection. Previous data showed that this response involves a rapid up-regulation of constitutive intercellular cell adhesion molecule-1 (ICAM-1) and migration of inflammatory cells into the cornea. In contrast, in aged mice, there is no up-regulation of corneal ICAM-1 inflammatory cell infiltration into the cornea is delayed, and the cornea perforates. Therefore, the aim of this study was to test whether specific cytokines which up-regulate ICAM-1 expression differ in young and aged mice. Corneas of young (6- to 8-week-old) and aged (1- to 2-year-old) mice were scarified and inoculated with P. aeruginosa. The eyes were graded for pathologic changes (score 0 to +4); at 6, 12, 24, and 48 h postinfection (p.i.), six mite fi om each age group were sacrificed. Three corneas from each respective roup were excised for quantitation of interleukin-1 beta (IL-1 beta), tumor necrosis factor alpha, and gamma interferon (IFN-gamma) by enzyme-linked immunosorbent assay. The remaining three corneas from each age group were harvested for quantitation of viable bacteria by dir-ed plate count determination and for infiltrating polymorphonuclear leukocytes (PMNs) by a myeloperoxidase (MPO) assay. Compared to those of young mice, the corneas of infected aged mice had less IL-1 beta at 6 h p,i. (P less than or equal to 0.04) and less IFN-gamma at 12 to 48 h p.i. (P less than or equal to 0.05). Also, compared to those of young mice, corneas of aged mice had fewer PMNs (P less than or equal to 0.008) by the MPO assay at 6 h p.i. and more viable bacteria (P less than or equal to 0.01) per cornea by plate count determination at 23 h p.i. These data suggest that the lack of up-regulation of ocular ICAM-1 in aged mire may reflect a reduction in both IL-1 beta and IFN-gamma levels in the infected cornea. Consequently, a sufficient number of PMNs and other inflammation cells fail to rapidly migrate into the infected corneas of aged mice, the bacterial load is initially greater than that in young mice, and the cornea perforates.