Role of a Reduction of Cytokine Levels in Isoflurane-mediated Protection from Endotoxin-induced Lung Injury

Abstract

Institute of Child Health, University of Liverpool, Liverpool, United Kingdom. michael_eisenhut@yahoo.comReutershan et al. 1reported on the finding of reduced endotoxin-induced acute lung injury in mice pretreated with isoflurane. In their investigation of the underlying cause of this phenomenon, the authors focused on neutrophil recruitment and chemokine concentrations. They found a reduction of neutrophil recruitment and CXCL1 and CXCL2/3 chemokine concentrations in the lungs of isoflurane-treated mice. Previous studies have not established a causal link between chemokine levels or the associated neutrophil accumulation and endotoxin-induced lung injury. There is, however, evidence that the cytokines tumor necrosis factor and interleukin 1 are involved in a reduction of alveolar ion and the associated fluid transport and hence pulmonary edema clearance.2,3Particularly tumor necrosis factor has been strongly implicated in the pathogenesis of pulmonary edema, and its effect is mediated by nitric oxide.2,4Tumor necrosis factor–induced nitric oxide leads thereby to a reduction of the activity of the alveolar epithelial sodium channel and the basolateral sodium potassium adenosine triphosphatase, which are essential for alveolar sodium and fluid transport.2Isoflurane has been shown to reduce plasma interleukin 1β and tumor necrosis factor levels significantly in endotoxemic rats.5The underlying cause for this effect has been investigated and found to be an inhibition of nuclear transcription factor KB.6The reduction in chemokine levels and subsequently neutrophil accumulation may be only a reflection of this inhibition of nuclear transcription factor KB rather than causally related to lung injury reduction, because chemokine genes are part of the array of genes regulated by this transcriptional factor.7Future studies on the protective effect of isoflurane against lung injury must correlate its effect on tumor necrosis factor and interleukin-1 levels with measures of pulmonary edema clearance.Institute of Child Health, University of Liverpool, Liverpool, United Kingdom. michael_eisenhut@yahoo.com