Khoury Paneez, Baroody Fuad M, Klemens James J, Thompson Kenneth, Naclerio Robert M
Department of Surgery, Section of Otolaryngology-Head and Neck Surgery, The University of Chicago, Illinois 60637, USA.
Ann Allergy Asthma Immunol. 2006 Sep;97(3):329-35. doi: 10.1016/S1081-1206(10)60797-1.
In mice, allergic rhinitis augments the infectious and inflammatory response to Streptococcus pneumoniae-induced sinusitis.
To investigate the effects of cysteinyl leukotriene antagonism on the severity of bacterial infection.
We performed 3 parallel, placebo-controlled experiments. In the first, mice were ovalbumin sensitized and ovalbumin challenged to show the effects of montelukast on the allergic inflammation; in the second, we evaluated the effect of montelukast on S. pneumoniae infection; in the third, we used mice that were both allergic and infected. Montelukast was given starting 2 days after sensitization until the day before euthanasia. One day after drug treatment began, the mice were inoculated intranasally with S. pneumoniae in the infected groups. Nasal hypersensitivity was measured with histamine challenges before the first sensitization and on the day before euthanasia. On the fifth day after infection, mice were euthanized, nasal lavage was performed, bacteria were cultured, and inflammatory cells in the sinuses were quantified.
Mice that were infected only tended toward having increased bacterial counts from nasal lavage in the montelukast-treated group. The mice that were allergic and infected experienced significantly higher bacterial counts (P < .05). All 3 montelukast treatment groups had significantly decreased eosinophil counts as well as T-lymphocyte counts.
Montelukast reduces the manifestations of allergic rhinitis in mice. Surprisingly, montelukast led to an increase in bacterial growth in infected mice. This suggests an effect of the cysteinyl leukotrienes on the innate response to bacterial infection.
在小鼠中,过敏性鼻炎会增强对肺炎链球菌诱导的鼻窦炎的感染和炎症反应。
研究半胱氨酰白三烯拮抗剂对细菌感染严重程度的影响。
我们进行了3项平行的、安慰剂对照实验。第一项实验中,用卵清蛋白对小鼠进行致敏和激发,以显示孟鲁司特对过敏性炎症的影响;第二项实验中,评估孟鲁司特对肺炎链球菌感染的影响;第三项实验中,使用既过敏又感染的小鼠。从致敏后第2天开始给予孟鲁司特,直至安乐死前一天。药物治疗开始后1天,感染组小鼠经鼻接种肺炎链球菌。在首次致敏前和安乐死前一天,用组胺激发试验测量鼻超敏反应。感染后第5天,对小鼠实施安乐死,进行鼻腔灌洗,培养细菌,并对鼻窦中的炎性细胞进行定量分析。
仅感染的小鼠,孟鲁司特治疗组鼻腔灌洗中的细菌计数有增加趋势。既过敏又感染的小鼠细菌计数显著更高(P <.05)。所有3个孟鲁司特治疗组的嗜酸性粒细胞计数和T淋巴细胞计数均显著降低。
孟鲁司特可减轻小鼠过敏性鼻炎的表现。令人惊讶的是,孟鲁司特导致感染小鼠的细菌生长增加。这表明半胱氨酰白三烯对细菌感染的固有反应有影响。