Amiodarone causes decreased cell-mediated immune responses and inhibits the phospholipase C signaling pathway

Abstract

Amiodarone can cause pulmonary toxicity along with an increase in phospholipid in macrophages, lymphocytes, and other cell types. Phospholipid accumulates because amiodarone inhibits the lysosomal phospholipases A1 and A2. Since a wide array of cells are affected by amiodarone and because amiodarone might inhibit other phospholipases, we postulated that cellular functions might be affected. Therefore, the major focus of this study was to determine whether amiodarone inhibited cellular functions. We found that alveolar macrophages isolated from drug-fed rats were significantly less phagocytic, and that the rats had significantly depressed delayed-type hypersensitivity responses. Spleen cells isolated from the drug-fed rats also had severely depressed mitogen responses. Since the spleen cell proliferative response could be partially restored by stimulating the cells with ionomycin and phorbol myristate acetate, we postulated that amiodarone was inhibiting phospholipase C. To substantiate this hypothesis, we found that amiodarone could directly inhibit phospholipase C in vitro. We conclude that amiodarone affects both phagocytic responses and the development of cell-mediated immunity and that the lack of these normal responses could exacerbate amiodarone toxicity. One possible mechanism for decreased cellular functions may be the inhibition of phospholipase C. However, further studies are necessary to confirm this finding.

Relative Perioperative Bradycardia Does Not Lead to Adverse Outcomes After Cardiac Transplantation

“…This implies a possible immunomodulatory role for amiodarone. Several studies have demonstrated that amiodarone can effect cellular and innate immunity, responses to infections and the development of autoimmunity (11)(12)(13)28). Thus, amiodarone may have immune-altering properties that may interfere in a recipient's response to alloantigens.…”

Preventive Effect of Amiodarone During Acute Period in Isoproterenol-Induced Myocardial Injury in Wistar Rats

“…It is an effective antiarrhythmic agent and is used to treat a wide variety of ventricular and supraventricular tachyarrhythmias [1]; it is considered the gold standard for the pharmacological treatment of life-threatening ventricular tachyarrhythmias in high-risk patients [2]. This drug can also modulate phospholipid metabolism [3] and inhibit phospholipase A1, A2 and phospholipase C [4]. Phospholipase enzyme plays a role in the production of inflammatory mediators during arachidonic acid metabolism.…”

Modulation of both activator protein-1 and nuclear factor-kappa B signal transduction of human T cells by amiodarone

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