CHARACTERIZATION OF AMIODARONE PNEUMONITIS AS RELATED TO INFLAMMATORYCELLS AND SURFACTANT APOPROTEIN

Study objective: To characterize the inflammation observed in amiodaro ne-induced pneumonitis. Design: The density of inflammatory cells in B AL fluid (BALF) and lung interstitium was quantified in a rat model of amiodarone pneumonitis, Immunoperoxidase staining for surfactant apop rotein was evaluated in lung tissue. Animals and interventions: Male F ischer 344 rats weighting 170 to 180 g received amiodarone, 150 mg/kg/ d, suspended in 0.5% methylcellulose by gavage 5 d/wk. Control animals were given only methylcellulose, Rats were killed after 3, 5, 7, 9, a nd 12 weeks. Histologic sections were prepared for hematoxylin-eosin s taining and the immunoperoxidase method. Measurements and results: Sig nificant positive correlations between the density of neutrophils in B ALF and the interstitium were seen at 5 weeks (r=0.90, p<0.05) and 7 w eeks (r=0.90, p<0.05), Significant positive correlations were observed between the density of lymphocytes in BALF and the interstitium at 9 weeks (r=0.90, p<0.05) and 12 weeks (r=0.90, p<0.05). The density of t ype II pneumocytes was significantly increased in the amiodarone-fed r ats, Extracellular surfacant apoprotein was found in the alveolar spac e and the cytoplasm of type II pneumocytes, Clara cells, and large, fo amy macrophages throughout drug treatment. Extracellular surfactant ap oprotein filled some alveoli at 9 weeks, Conclusions: The density of l ymphocytes and neutrophils increased significantly in the BALF and the lung interstitium throughout amiodarone administration. The relations hip between the density of lymphocytes in BALF and in the interstitium differed from that of neutrophils. In addition, amiodarone caused hyp erplasia of type II pneumocytes and deposition of conglomerated, extra cellular surfactant apoprotein in the alveolar space.