title: Halogenated anesthetics reduce interleukin-1beta-induced cytokine secretion by rat alveolar type II cells in primary culture.
abstract: BACKGROUND
  Alveolar epithelial type II (AT II ) cells participate in the intraalveolar cytokine network by secreting cytokines and are widely exposed to volatile anesthetics during general anesthesia. The aim of the current study was to evaluate the effects of halothane, enflurane, and isoflurane on rat AT II cell cytokine secretions in AT II primary cell cultures.
  
  
  METHODS
  Alveolar epithelial type II primary cell cultures were obtained from adult rat lungs. AT II cells were stimulated by recombinant murine interleukin-1beta (rmIL-1beta) to mimic an inflammatory response, and immediately exposed for various duration to different concentration of halothane, enflurane, or isoflurane. Interleukin-6, macrophage inflammatory protein-2 (MIP-2), and monocyte chemoattractant protein-1 (MCP-1) protein concentrations were then measured in cell culture supernatants. Recombinant mIL-1beta-stimulated AT II cells exposed to air served as control.
  
  
  RESULTS
  Halothane, isoflurane, and enflurane (1 minimum alveolar concentration [MAC], 4 h) decreased rmIL-1beta-stimulated AT II cell secretions of interleukin-6, MIP-2, and MCP-1, but did not modify total protein secretion. Halothane exposure decreased rmIL-1beta-stimulated AT II cell secretions of interleukin-6, MIP-2, and MCP-1 in a dose- and time-dependent manner. Total protein concentrations remained unchanged except AT II 1.5 MAC of halothane, and no cytotoxic effect could be evidenced by lactate dehydrogenase release. These effects were transient as rmIL-1beta-stimulated AT II cell secretions of interleukin-6 and MIP-2 progressively reached control values between 4 and 24 h after the end of halothane exposure. However, MCP-1 inhibition persisted until 24 h. rmIL-1beta-induced MIP-2 and tumor necrosis factor-alpha mRNA expression were decreased by 36 and 24%, respectively, after halothane exposure.
  
  
  CONCLUSIONS
  The current study shows that exposure of rmIL-1beta-stimulated AT II cells to volatile anesthetics reversibly alters their cytokine secretion. Therefore, volatile anesthesia, by modulating pulmonary epithelial cell secretion of inflammatory cytokines, might affect the lung inflammatory response.
authors.affiliation: Institut National de la Santé Et de la Recherche Médicale, Unité 408, Faculté de Médecine Xavier Bichat, Département d'Anesthésie-Réanimation Chirurgicale, Centre Hospitalo-Universitaire Bichat Claude Bernard, Paris, France. giraud@igr.fr
authors.forename: Olivier
authors.initials: O
authors.lastname: Giraud
authors.forename: Serge
authors.initials: S
authors.lastname: Molliex
authors.forename: Corinne
authors.initials: C
authors.lastname: Rolland
authors.forename: Véronique
authors.initials: V
authors.lastname: Leçon-Malas
authors.forename: Jean-Marie
authors.initials: JM
authors.lastname: Desmonts
authors.forename: Michel
authors.initials: M
authors.lastname: Aubier
authors.forename: Monique
authors.initials: M
authors.lastname: Dehoux
mesh_terms: D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000096:biosynthesis; D016207:Cytokines / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004737:Enflurane / Q000494:pharmacology; D006221:Halothane / Q000494:pharmacology; D007375:Interleukin-1 / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D015850:Interleukin-6 / Q000096:biosynthesis; D007530:Isoflurane / Q000494:pharmacology; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D011014:Pneumonia / Q000378:metabolism / Q000473:pathology; D014176:Protein Biosynthesis; D011650:Pulmonary Alveoli / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D011994:Recombinant Proteins / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D018685:Anesthetics, Inhalation; D018932:Chemokine CCL2; D016207:Cytokines; D007375:Interleukin-1; D015850:Interleukin-6; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D004737:Enflurane; D007530:Isoflurane; D007770:L-Lactate Dehydrogenase; D006221:Halothane