• Yong Song, Yi Shi, Alden H Harken, Xianzhong Meng, and Christopher D Raeburn.
• Department of Respiratory Medicine, Nanjing General Hospital of PLA, Nanjing 210002, China.
• Zhonghua Yi Xue Za Zhi. 2003 Apr 25; 83 (8): 691-4.

ObjectiveTo examine the temporal relationship of pulmonary TNF-alpha production to acute lung injury (ALI) during hemorrhagic shock (HS).MethodsHS was induced in mice by removal of 30% of calculated total blood volume. Lung TNF-alpha was measured by ELISA. Lung neutrophil accumulation was detected by immunofluorescent staining, and pulmonary microvascular permeability was assessed using Evans blue dye.ResultsWhile HS induced a slight and transient increase in lung TNF-alpha, neutrophil accumulation preceded the change in lung TNF-alpha. However, lung neutrophil accumulation and the increase in microvascular permeability were abrogated in TNF-alpha knockout mice, and both were restored by administration of low dose TNF-alpha to TNF-alpha knockout mice prior to HS. Both neutrophil accumulation and microvascular leak were abrogated in p55 TNF-alpha receptor knockout mice, while p75 TNF-alpha receptor knockout mice behaved similar to wild type.ConclusionA low level of pulmonary TNF-alpha is sufficient to mediate HS-induced acute lung injury and that the p55 TNF-alpha receptor plays a dominant role in regulating the pulmonary inflammatory response to HS. The results suggest that anti-TNF-alpha strategies for the control of the pulmonary inflammatory response to HS can be directed toward antagonizing the p55 TNF-alpha receptor.

22 keywords...

hide…