Inhibition of neutrophil activation by volatile anesthetics decreases adhesion to cultured human endothelial cells

Background: Polymorphonuclear leukocytes (neutrophils, PMNs) have been show n to mediate vascular and tissue injury, leading to so-called systemic infl ammatory response syndrome. The authors evaluated the effect of volatile an esthetics on neutrophil adhesion to human endothelial cells, focusing on wh ether the inhibitory effect observed is linked to an alteration in the func tion of endothelial cells or neutrophils. Methods: The adhesion of human PMNs was quantified using cultured human umb ilical vein endothelial cells (HUVECs). The increase in the number of adher ing PMNs was assessed when HUVECs (with 1 mM hydrogen peroxide), PMNs (with 10 aw N-formyl-methionyl-leucyl-phenylalanine), or both were prestimulated . To determine the influence of volatile anesthetics on the adhesion of PMN s, the experiments were performed in the absence or presence of 0.5, 1, and 2 minimum alveolar concentration halothane, isoflurane, or sevoflurane, wh ereby HUVECs, PMNs, or both were pretreated with gas. Results: Activation of HUVECs with hydrogen peroxide or stimulation of PMNs with N-formyl-methionyl-leucyl-phenylalanine resulted in a 2.5-fold increa se in PMN adhesion. Preincubation of PMNs, separately, with halothane, isof lurane, or sevoflurane, respectively, abolished enhanced neutrophil adhesio n to hydrogen peroxide-activated HUVECs and adhesion of PMNs prestimulated with N-formyl-methionyl-leucyl-phenylalanine to unstimulated HUVECs (maxima l effect at 1 minimum alveolar concentration). No decrease in adhesion was detected when only HUVECs were pretreated with volatile anesthetics. Additi onal exposure of HUVECs and PMNs to volatile anesthetics had no inhibitory effect on adhesion greater than that seen when only PMNs were treated. Appr opriately, the volatile anesthetics abolished the upward regulation of the adhesion molecule CD11b on PMNs (as evaluated at 1 minimum alveolar concent ration each), whereas 1 minimum alveolar concentration halothane failed to affect the expression of P-selectin, an adhesion molecule on endothelial ce lls. Conclusions: This study indicates that halothane, isoflurane, and sevoflura ne inhibit neutrophil adhesion to human endothelial cells at concentrations relevant to anesthesia in a static system, The effects appear to be mediat ed by inhibition of PMN activation; that is, by attenuating the upward regu lation of neutrophil CD11b.