Isoflurane inhibits neutrophil recruitment in the cutaneous Arthus reaction model

Neutrophil recruitment to the inflammatory sites is regulated by a variety of adhesion molecules including beta 2 integrins. The dependency of neutrophil recruitment on beta 2 integrins is variable in different tissues, but has not yet been verified in the cutaneous passive reverse Arthus reaction. We examined this question and also evaluated the impact of isoflurane on neutrophil recruitment to the skin because we previously showed in vitro that isoflurane binds and inhibits beta 2 integrins. The dependency on beta 2 integrins in neutrophil recruitment to the skin in the Arthus reaction was examined using alpha L, alpha M and beta 2 knockout mice. Then, we evaluated the effect of isoflurane on neutrophil recruitment to the skin. In addition, the effects of isoflurane on neutrophil binding to intercellular adhesion molecule-1 (ICAM-1), one of the beta 2 integrin ligands, were studied in vitro using cell adhesion assays. Neutrophil recruitment to the skin in the Arthus reaction model was totally dependent on beta 2 integrins, as beta 2 knockout mice completely abolished it. However, the defect of only one of the beta 2 integrins was not sufficient to abolish neutrophil recruitment. Isoflurane reduced neutrophil recruitment to the skin by approximately 90 %. Also, isoflurane inhibited neutrophil adhesion to beta 2 integrin ligand ICAM-1. We demonstrated that (1) neutrophil recruitment to the skin was totally dependent on beta 2 integrins, and (2) isoflurane significantly impaired neutrophil recruitment. Based on the previous studies on the contribution of other adhesion molecules in neutrophil recruitment, it is likely that isoflurane at least partially affects on beta 2 integrins in this model.