Characterization of amiodarone pneumonitis as related to inflammatory cells and surfactant apoprotein.
OBJECTIVE
To characterize the inflammation observed in amiodarone-induced pneumonitis.


METHODS
The density of inflammatory cells in BAL fluid (BALF) and lung interstitium was quantified in a rat model of amiodarone pneumonitis. Immunoperoxidase staining for surfactant apoprotein was evaluated in lung tissue.


METHODS
Male Fischer 344 rats weighing 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, and 12 weeks. Histologic sections were prepared for hematoxylin-eosin staining and the immunoperoxidase method.


RESULTS
Significant positive correlations between the density of neutrophils in BALF and the interstitium were seen at 5 weeks (r=0.90, p<0.05) and 7 weeks (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 type II pneumocytes was significantly increased in the amiodarone-fed rats. Extracellular surfactant apoprotein was found in the alveolar space and the cytoplasm of type II pneumocytes, Clara cells, and large, foamy macrophages throughout drug treatment. Extracellular surfactant apoprotein filled some alveoli at 9 weeks.


CONCLUSIONS
The density of lymphocytes and neutrophils increased significantly in the BALF and the lung interstitium throughout amiodarone administration. The relationship between the density of lymphocytes in BALF and in the interstitium differed from that of neutrophils. In addition, amiodarone caused hyperplasia of type II pneumocytes and deposition of conglomerated, extracellular surfactant apoprotein in the alveolar space.
Nagata
N
N
Division of Respiratory Diseases, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan.
Suematsu
R
R
Yoshii
C
C
Miyazaki
H
H
Sueishi
K
K
Kido
M
M
D000638:Amiodarone / Q000009:adverse effects*; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000009:adverse effects*; D001059:Apoproteins / Q000032:analysis*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D004396:Coloring Agents; D003593:Cytoplasm / Q000648:ultrastructure; D004195:Disease Models, Animal; D004801:Eosine Yellowish-(YS); D005110:Extracellular Space / Q000737:chemistry; D005456:Fluorescent Dyes; D005487:Foam Cells / Q000473:pathology; D006416:Hematoxylin; D006965:Hyperplasia; D007124:Immunoenzyme Techniques; D007958:Leukocyte Count; D007962:Leukocytes / Q000473:pathology*; D008168:Lung / Q000737:chemistry / Q000187:drug effects / Q000473:pathology; D018655:Lymphocyte Count; D008214:Lymphocytes / Q000473:pathology; D016676:Macrophages, Alveolar / Q000473:pathology; D008297:Male; D008747:Methylcellulose / Q000494:pharmacology; D009504:Neutrophils / Q000473:pathology; D010592:Pharmaceutic Aids / Q000494:pharmacology; D011014:Pneumonia / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D011650:Pulmonary Alveoli / Q000737:chemistry / Q000187:drug effects / Q000473:pathology; D011663:Pulmonary Surfactants / Q000737:chemistry*; D051381:Rats; D011916:Rats, Inbred F344; D013997:Time Factors
D000889:Anti-Arrhythmia Agents; D001059:Apoproteins; D004396:Coloring Agents; D005456:Fluorescent Dyes; D010592:Pharmaceutic Aids; D011663:Pulmonary Surfactants; D008747:Methylcellulose; D000638:Amiodarone; D004801:Eosine Yellowish-(YS); D006416:Hematoxylin