Tekkanat Kim K, Maassab Hussein, Miller Allison, Berlin Aaron A, Kunkel Steven L, Lukacs Nicholas W
Department of Pediatrics, University of Michigan Medical School, Ann Arbor, USA.
Eur J Immunol. 2002 Nov;32(11):3276-84. doi: 10.1002/1521-4141(200211)32:11<3276::AID-IMMU3276>3.0.CO;2-5.
Respiratory syncytial virus (RSV) is a respiratory pathogen that causes significant morbidity in infants and young children. The importance of chemokines during RSV infection for respiratory symptoms has not been fully elucidated. The current study examined the effect of RANTES (CCL5) on airway pathophysiology after RSV infection. BALB/c mice produce RANTES (CCL5) after RSV infection that correlates with the changes in pathophysiology. Animals treated with anti-RANTES (CCL5) antibody demonstrated significant decreases in airway hyperreactivity (AHR). Delayed treatment with anti-RANTES (CCL5) at day 5 of infection also significantly reduced development of AHR on day 9 of infection, suggesting that RANTES (CCL5) may be a target in established disease. Determination of Th1/Th2-associated cytokine patterns indicated that anti-RANTES (CCL5) treatment increased IL-12 production, thus altering the lung environment. The assessment of RANTES (CCL5) production in vitro and in vivo demonstrated that it was regulated by IL-13, a cytokine that is related to RSV-induced AHR in this mouse model. These data show that RANTES (CCL5) is an important mediator of the pathophysiological responses seen in RSV infection.
呼吸道合胞病毒(RSV)是一种呼吸道病原体,可导致婴幼儿出现严重发病情况。趋化因子在RSV感染期间对呼吸道症状的重要性尚未完全阐明。当前研究检测了RANTES(CCL5)对RSV感染后气道病理生理学的影响。BALB/c小鼠在RSV感染后产生RANTES(CCL5),这与病理生理学变化相关。用抗RANTES(CCL5)抗体处理的动物气道高反应性(AHR)显著降低。在感染第5天用抗RANTES(CCL5)进行延迟处理也显著降低了感染第9天AHR的发展,这表明RANTES(CCL5)可能是已确诊疾病的一个靶点。对Th1/Th2相关细胞因子模式的测定表明,抗RANTES(CCL5)处理增加了IL-12的产生,从而改变了肺部环境。在体外和体内对RANTES(CCL5)产生的评估表明,它受IL-13调节,IL-13是一种在该小鼠模型中与RSV诱导的AHR相关的细胞因子。这些数据表明,RANTES(CCL5)是RSV感染中所见病理生理反应的重要介质。