Section of Medical Sciences, Patras Highest Institute of Educational Technology, 7 Aratou Street, 26221 Patras, Greece
Received August 5, 2004; revised August 5, 2004; accepted August 13, 2004 * Corresponding author. Tel./Fax: +30 2610 279579 (E-mail: ngkounis{at}otenet.gr).
In the excellent paper by Dernellis and Panaretou1 it was shown that lowering the C-reactive protein (CRP) to <0.62 and <1.56/dl by giving 16 mg methylprednisolone for 4 weeks tapering it to 4 mg for 4 months could bring reduction in the recurrent and permanent atrial fibrillation (AF), respectively. The beneficial effects of glucocorticoid therapy were attributed to the alleviation of inflammatory processes accompanying AF. However, these authors did not elaborate in the mechanism of action of glucocorticoids in preventing the recurrent and permanent AF.
We would like to point out that although the mechanism of glucocorticoid action has not yet been completely elucidated, these drugs can suppress the release of arachidonic acid from cell membrane and inhibit eicosanoid biosynthesis in human macrophages. In a recent report,2 the administration of methylprednisolone caused a dose-dependent inhibition of inducible prostanoid biosynthesis, presumably through down-regulation of monocyte COX-2 expression. The suppression of arachidonic acid release is mediated through inhibition of phospholipase A2.3 Furthermore, glucocorticoids may also inhibit phospholipase A2 activation and arachidonic acid release through a glucocorticoid receptor-dependent, transcription-independent mechanism. Glucocorticoids may also reduce inflammation by inducing cell apoptosis via an autocrine or paracrine pathway involving the up-regulation of the death receptor CD95 and its ligand CD95L on cell membranes. Studies in humans and in animals suggest that the anti-inflammatory effect might occur through induction of the synthesis of a family of proteins such as annexins, also called lipocortins, which have a pivotal role in modulating inflammatory cell activation, adhesion molecule expression, and transmigratory and phagocytic functions.3
Kounis syndrome4 is the coincidental occurrence of allergic or hypersensitivity reactions with acute coronary syndromes leading to allergic angina and/or allergic myocardial infarction. It is caused by certain conditions, environmental exposures, poisons, venoms and drugs, via inflammatory mediators including histamine, tryptase, chymase and arachidonic acid products such as leukotrienes. The latter have been characterised as proinflammatory, prothrombotic lipid-derived mediators that may play a part in arrhythmogenesis and their biosynthesis can be suppressed by glucocorticoids.5
Corticosteroids, through reduction of the transcription of several proinflammatory cytokines, including CRP, could reduce the risk of myocardial infarction by 50% according to a recent report6 and can successfully treat refractory vasospastic angina according to another report.7
Therefore, reducing the transcription of proinflammatory cytokines such as CRP and inhibiting the metabolism of arachidonic acid by glucocorticoids seems to be a potential therapeutic strategy for the vexing and so common arrhythmia of AF.
References