Effects of amiodarone-induced phospholipidosis on pulmonary host defense functions in rats.
The effect of the induction of pulmonary phospholipidosis by amiodarone on selected pulmonary host defense functions was studied in male Fischer-344 rats. One week of daily amiodarone treatment resulted in a 4.5-fold increase in total phospholipid in alveolar macrophages recovered from the lungs by bronchoalveolar lavage. The presence of the phospholipidosis had no effect on the phagocytosis of heat-killed yeast cells, the induction of luminol-dependent chemiluminescence, or the spontaneous release of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha), or spontaneous and LPS-stimulated release of IL-1 by alveolar macrophages in vitro. In contrast, the LPS-stimulated release of IL-6 and TNF-alpha by phospholipidotic alveolar macrophages was enhanced compared with control cells. The pulmonary clearance of Listeria monocytogenes following intratracheal administration of the bacteria was not affected by the phospholipidotic condition. It appears that, in the context of the functions studied, the induction of pulmonary phospholipidosis by amiodarone does not impair pulmonary host defense processes in rats, and may actually be associated with the augmentation of some activities.
Reasor
M J
MJ
Department of Pharmacology and Toxicology, Robert C. Byrd Health Sciences Center of West Virginia University, Morgantown, 26506-9223, USA.
McCloud
C M
CM
DiMatteo
M
M
Schafer
R
R
Ima
A
A
Lemaire
I
I
D000638:Amiodarone / Q000633:toxicity*; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000633:toxicity*; D007113:Immunity, Innate / Q000187:drug effects*; D007378:Interleukins / Q000378:metabolism; D008064:Lipidoses / Q000139:chemically induced*; D008088:Listeriosis / Q000503:physiopathology; D008163:Luminescent Measurements; D008168:Lung / Q000187:drug effects* / Q000276:immunology; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000502:physiology; D008297:Male; D010743:Phospholipids / Q000378:metabolism*; D011650:Pulmonary Alveoli / Q000502:physiology; D051381:Rats; D011916:Rats, Inbred F344; D014409:Tumor Necrosis Factor-alpha / Q000187:drug effects / Q000378:metabolism
D000889:Anti-Arrhythmia Agents; D007378:Interleukins; D010743:Phospholipids; D014409:Tumor Necrosis Factor-alpha; D000638:Amiodarone