title: Morphological and functional determinants of fluoxetine (Prozac)-induced pulmonary disease in an experimental model.
abstract: Fluoxetine treatment effects were determined by evaluating respiratory mechanics (elastance/resistance) and exhaled nitric oxide, as well as mononuclear and polymorphonuclear cell recruitment into the lungs, in an experimental guinea pig model. Guinea pigs were divided into four groups: Fl (fluoxetine only, n=7); Fl+Sw (fluoxetine and forced swimming, n=7); Ns+Sw (normal saline and forced swimming, n=8); and Ns (normal saline only, n=8). Treated animals received oral fluoxetine (10 mg/(kg day)) for 30 consecutive days. On day 31, all animals were anesthetized and mechanically ventilated so that respiratory system elastance and resistance, as well exhaled nitric oxide, could be determined. The lungs were then excised en bloc for histological and immunohistochemical evaluation. Forced swimming induced bronchodilation in untreated animals and bronchoconstriction in fluoxetine-treated animals. Fluoxetine treatment was also associated with mononuclear infiltration (predominantly into alveolar walls) and neutrophil recruitment. In addition, levels of exhaled nitric oxide, an inflammatory marker, were higher in fluoxetine-treated animals. Swimming-induced stress also amplified mononuclear cell recruitment to the lungs. These results show that, in this experimental model, fluoxetine treatment reproduces the pathology of chronic interstitial pneumonia in humans.
authors.affiliation: Department of Pathology, University of São Paulo School of Medicine, Brazil. marco_capelozzi@uol.com.br
authors.forename: Marco A
authors.initials: MA
authors.lastname: Capelozzi
authors.forename: Edna A
authors.initials: EA
authors.lastname: Leick-Maldonado
authors.forename: Edwin R
authors.initials: ER
authors.lastname: Parra
authors.forename: Mílton A
authors.initials: MA
authors.lastname: Martins
authors.forename: Iolanda F L C
authors.initials: IF
authors.lastname: Tibério
authors.forename: Vera L
authors.initials: VL
authors.lastname: Capelozzi
mesh_terms: D000403:Airway Resistance / Q000187:drug effects; D000818:Animals; D018687:Antidepressive Agents, Second-Generation / Q000494:pharmacology / Q000627:therapeutic use; D016084:Bronchoconstriction / Q000187:drug effects*; D004195:Disease Models, Animal; D004548:Elasticity / Q000187:drug effects; D005473:Fluoxetine / Q000494:pharmacology* / Q000627:therapeutic use; D006168:Guinea Pigs; D017254:Leukemic Infiltration / Q000139:chemically induced / Q000503:physiopathology; D017563:Lung Diseases, Interstitial / Q000139:chemically induced* / Q000503:physiopathology; D009569:Nitric Oxide / Q000378:metabolism; D015656:Respiratory Mechanics / Q000187:drug effects*; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D018709:Statistics, Nonparametric; D013315:Stress, Psychological / Q000188:drug therapy; D013550:Swimming / Q000502:physiology / Q000523:psychology
chemical_list: D018687:Antidepressive Agents, Second-Generation; D005473:Fluoxetine; D009569:Nitric Oxide; D017367:Selective Serotonin Reuptake Inhibitors