title: Effects of in vitro amiodarone exposure on alveolar macrophage inflammatory mediator production.
abstract: Administration of amiodarone, although often lifesaving, is associated with pulmonary side effects. Patients with amiodarone pulmonary toxicity can present with either a chronic disorder that suggests pulmonary fibrosis or a more acute process. Mechanisms of acute pulmonary injury resulting from amiodarone are unclear. Previous studies have demonstrated that the drug is preferentially concentrated in alveolar macrophages. In the present study, the authors examined whether in vitro exposure to amiodarone resulted in alteration of rat alveolar macrophage superoxide, leukotriene B4, or fibronectin release. In addition, the authors assessed whether macrophages were ultrastructurally altered by in vitro amiodarone exposure. Twenty four hour exposure to therapeutic tissue concentrations of amiodarone resulted in enhancement of phorbol myristate acetate-stimulated macrophage superoxide release. In addition, 48 hours exposure to amiodarone caused a dose-dependent inhibition of spontaneous fibronectin release by macrophages. Macrophages exposed to 48 hours of 10 micrograms/ml amiodarone were ultrastructurally abnormal, containing lamellar inclusions and demonstrating a large degree of vacuolization. The authors concluded that alveolar macrophages are very sensitive to therapeutic tissue concentrations of amiodarone. Alteration of macrophage mediator release by amiodarone may be one mechanism for lung damage induced by the drug.
authors.affiliation: Pulmonary Section, Yale University School of Medicine, New Haven, Connecticut.
authors.forename: R J
authors.initials: RJ
authors.lastname: Zitnik
authors.forename: J A
authors.initials: JA
authors.lastname: Cooper
authors.forename: J A
authors.initials: JA
authors.lastname: Rankin
authors.forename: J
authors.initials: J
authors.lastname: Sussman
mesh_terms: D000638:Amiodarone / Q000009:adverse effects*; D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects; D005353:Fibronectins / Q000378:metabolism; D066298:In Vitro Techniques; D007249:Inflammation / Q000473:pathology; D007975:Leukotriene B4 / Q000378:metabolism; D016676:Macrophages, Alveolar / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D008297:Male; D008854:Microscopy, Electron; D051381:Rats; D013481:Superoxides / Q000378:metabolism
chemical_list: D005353:Fibronectins; D013481:Superoxides; D007975:Leukotriene B4; D000638:Amiodarone