van der Sluijs Koenraad F, Nijhuis Monique, Levels Johannes H M, Florquin Sandrine, Mellor Andrew L, Jansen Henk M, van der Poll Tom, Lutter René
Department of Pulmonology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
J Infect Dis. 2006 Jan 15;193(2):214-22. doi: 10.1086/498911. Epub 2005 Dec 14.
Airway infection with influenza virus induces local expression of the tryptophan-catabolizing enzyme indoleamine 2,3-dioxygenase (IDO), which has been shown to enhance inflammatory mediator responses in vitro. Because secondary pneumococcal infections occurring shortly after recovery from influenza are associated with enhanced inflammatory responses, we hypothesized that IDO activity contributes to the enhanced response to bacterial challenges in mice previously infected with influenza virus.
On day 14 after influenza virus infection (with strain A/PR/8/34), C57Bl/6 mice were intranasally inoculated with 1 x 10(4) colony-forming units of S. pneumoniae (serotype 3). Matrix-driven delivery pellets that contained 70 mg of the IDO inhibitor 1-methyl-DL-tryptophan (MeTrp) released over a period of 7 days were subcutaneously implanted 48 h before pneumococcal infection.
MeTrp treatment resulted in a 20-fold reduction in pneumococcal outgrowth 48 h after bacterial inoculation. Remarkably, pulmonary levels of interleukin-10 and tumor necrosis factor-alpha were significantly reduced in mice treated with MeTrp.
Our data suggest that IDO expression during influenza virus infection alters the inflammatory response and facilitates the outgrowth of pneumococci during secondary bacterial pneumonia.
流感病毒引起的气道感染会诱导色氨酸分解代谢酶吲哚胺2,3-双加氧酶（IDO）的局部表达，体外实验已表明该酶可增强炎症介质反应。由于流感恢复后不久发生的继发性肺炎球菌感染与炎症反应增强有关，我们推测IDO活性有助于先前感染流感病毒的小鼠对细菌攻击的反应增强。
在感染甲型流感病毒A/PR/8/34 14天后，给C57Bl/6小鼠经鼻接种1×10⁴集落形成单位的肺炎链球菌（3型血清型）。在肺炎球菌感染前48小时，皮下植入基质驱动的给药微丸，其中含有70毫克IDO抑制剂1-甲基-DL-色氨酸（MeTrp），在7天内释放。
MeTrp治疗使细菌接种后48小时肺炎球菌的生长减少了20倍。值得注意的是，MeTrp治疗的小鼠肺部白细胞介素-10和肿瘤坏死因子-α水平显著降低。
我们的数据表明，流感病毒感染期间IDO的表达会改变炎症反应，并促进继发性细菌性肺炎期间肺炎球菌的生长。
