Isoflurane inhibits neutrophil recruitment in the cutaneous Arthus reaction model

• Published in: Journal of anesthesia 2013-04, Vol.27 (2), p.261-268
• Main Authors: Carbo, Carla, Yuki, Koichi, Demers, Melanie, Wagner, Denisa D., Shimaoka, Motomu
• Format: Article
• Language: English
• Subjects: Anesthesiology; Anesthetics, Inhalation - pharmacology; Animals; Arthus Reaction - pathology; Arthus Reaction - prevention & control; CD11b Antigen - genetics; CD11b Antigen - metabolism; Cell Adhesion - drug effects; Critical Care Medicine; Dosage and administration; Emergency Medicine; Flow Cytometry; In Vitro Techniques; Integrin beta Chains - pharmacology; Integrins; Intensive; Intercellular Adhesion Molecule-1 - metabolism; Isoflurane; Isoflurane - pharmacology; Medicine; Medicine & Public Health; Mice; Mice, Inbred C57BL; Mice, Knockout; Neutrophil Infiltration - drug effects; Neutrophils; Original Article; Pain Medicine; Peroxidase - metabolism; Physiological aspects; Skin - pathology
• ISSN: 0913-8668; 1438-8359
• DOI: 10.1007/s00540-012-1508-1

Purpose Neutrophil recruitment to the inflammatory sites is regulated by a variety of adhesion molecules including β2 integrins. The dependency of neutrophil recruitment on β2 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 β2 integrins. Methods The dependency on β2 integrins in neutrophil recruitment to the skin in the Arthus reaction was examined using αL, αM and β2 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 β2 integrin ligands, were studied in vitro using cell adhesion assays. Results Neutrophil recruitment to the skin in the Arthus reaction model was totally dependent on β2 integrins, as β2 knockout mice completely abolished it. However, the defect of only one of the β2 integrins was not sufficient to abolish neutrophil recruitment. Isoflurane reduced neutrophil recruitment to the skin by approximately 90 %. Also, isoflurane inhibited neutrophil adhesion to β2 integrin ligand ICAM-1. Conclusions We demonstrated that (1) neutrophil recruitment to the skin was totally dependent on β2 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 β2 integrins in this model.