Anesthetic Isoflurane Posttreatment Attenuates Experimental Lung Injury by Inhibiting Inflammation and Apoptosis

Li-Chao Hou,Ke-Lang Xie,Chun-Fang Gao,Jing-Lan Mu,Hui Wang,Jun-Tang Li,Li-Feng Wang,Xin Liu,Hui-Juan Chen,Nan-Lin Li,Wei Li

doi:10.1155/2013/108928

Abstract

We investigated the effect of 1.4% isoflurane (ISO) on the development of inflammation and apoptosis caused by zymosan (ZY) in mice. We found that ZY-challenged mice exhibited significant body weight loss, markedly high mortality, and significant lung injury characterized by the deterioration of histopathology, histologic scores, and wet-to-dry ratio after ISO treatment. ISO dramatically attenuated ZY-induced lung neutrophil recruitment and inflammation, as evidenced by the reduced levels of total cells, neutrophils, and proinflammatory cytokines (i.e., tumor necrosis factor-α, interleukin- (IL-) 1β, IL-6, and macrophage inflammatory protein-2) in bronchoalveolar lavage fluid and of their mRNA expression in lung tissues. ISO also inhibited ZY-induced expression and activation of nuclear factor-kappaB p65 and inducible nitric oxide synthase in pulmonary tissue. ZY administration also resulted in the upregulation of heme oxygenase-1 expression and activity in the lung, which was further enhanced by ISO treatment. Moreover, ISO markedly prevented ZY-induced pulmonary cell apoptosis in mice, as reflected by the decrease in expression of procaspase-8, procaspase-3, cleaved caspase-8, and cleaved caspase-3, as well as in caspase-3 activity and Bcl-2-associated X/B-cell lymphoma 2 ratio. These results indicate that ISO is a potential therapeutic drug for treating ZY-induced lung injury, and further investigations are warranted.

Highlights

Multiple organ dysfunction syndrome (MODS) is one of the most urgent and challenging public health problems worldwide
We found that the levels of the proinflammatory cytokines Tumor necrosis factor-α ZIGI (TNF-α), IL-1β, IL-6, and macrophage inflammatory protein-2 (MIP-2) in bronchoalveolar lavage fluid (BALF) substantially increased at 24 h in ZY-challenged mice, which were markedly downregulated by 1.4% ISO treatment
The BALF and pulmonary levels of these cytokines were almost not altered in sham-treated mice. These results demonstrated that 1.4% ISO treatment significantly prevented proinflammatory cytokine (TNF-α, IL-1β, IL-6, and MIP-2) upregulation in BALF and lung tissues of ZY-challenged mice

Summary

Introduction

Multiple organ dysfunction syndrome (MODS) is one of the most urgent and challenging public health problems worldwide. Lung tissue usually fails first in the development of MODS and intense inflammation, and inflammatory-stress-induced apoptosis is the main cause of lung injury [3,4,5]. The mechanism underlying inflammation-induced lung injury and appropriate treatment approaches are still unknown. In 1986, Goris et al [6] described a zymosan- (ZY-) induced generalized inflammation (ZIGI) model, which is recognized as the only model to share numerous characteristics with human MODS and has been adopted by other research groups [6] including our group [7]. ZY induces inflammation by upregulating a wide range of inflammatory mediators [8,9,10]. Intensive inflammation has been associated with apoptotic cell death [11]. ZY administration results in the upregulation of proapoptotic Fas ligand and altered balance between Bcl-2-associated X

Results

Discussion

Conclusion