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Effects of amiodarone-induced phospholipidosis on pulmonary host defense functions in rats
M J Reasor1, C M McCloud, M DiMatteo
1Department of Pharmacology and Toxicology, Robert C. Byrd Health Sciences Center of West Virginia University, Morgantown, 26506-9223, USA.
Abstract:
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.
Insights
Amiodarone-induced pulmonary phospholipidosis in rats did not impair key lung defense functions. However, it enhanced the release of certain inflammatory signals (IL-6, TNF-alpha) from lung immune cells.
Area of Science:
- Pulmonary toxicology
- Immunology
- Pharmacology
Background:
- Amiodarone, an antiarrhythmic drug, is known to cause pulmonary phospholipidosis.
- Pulmonary phospholipidosis involves the accumulation of phospholipids in alveolar macrophages.
- The impact of amiodarone-induced phospholipidosis on lung immune defenses remains unclear.
Purpose of the Study:
- To investigate the effects of amiodarone-induced pulmonary phospholipidosis on specific pulmonary host defense functions in rats.
- To assess the functional capacity of alveolar macrophages in the presence of amiodarone-induced phospholipidosis.
Main Methods:
- Male Fischer-344 rats were treated daily with amiodarone for one week.
- Pulmonary phospholipidosis was confirmed by measuring phospholipid content in alveolar macrophages obtained via bronchoalveolar lavage.
- In vitro assays evaluated phagocytosis, chemiluminescence, and cytokine release (IL-1, IL-6, TNF-alpha) from alveolar macrophages.
- Pulmonary clearance of intratracheally administered Listeria monocytogenes was assessed.
Main Results:
- Amiodarone treatment significantly increased phospholipid content in alveolar macrophages, confirming phospholipidosis.
- Phagocytosis, chemiluminescence, and spontaneous cytokine release (IL-1, IL-6, TNF-alpha) were unaffected.
- Lipopolysaccharide (LPS)-stimulated release of IL-6 and TNF-alpha was enhanced in phospholipidotic macrophages.
- Pulmonary clearance of Listeria monocytogenes was not altered by the phospholipidotic condition.
Conclusions:
- Amiodarone-induced pulmonary phospholipidosis in rats does not compromise major pulmonary host defense mechanisms studied.
- Specific inflammatory responses, including LPS-stimulated IL-6 and TNF-alpha release, were augmented.
- These findings suggest that amiodarone-induced phospholipidosis may not be detrimental to overall lung immune defense in this model.