Morphological and functional determinants of fluoxetine (Prozac)-induced pulmonary disease in an experimental model

Fluoxetine treatment effects were determined by evaluating respiratory mechanics (elastance/resi stance) and exhaled nitric oxide, as well as mononuclear and polymorphonuc tear 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. (c) 2006 Elsevier B.V. All rights reserved.