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(Circulation. 2003;107:55.)
© 2003 American Heart Association, Inc.

Clinical Investigation and Reports

Modulation of Aspirin-Insensitive Eicosanoid Biosynthesis by 6-Methylprednisolone in Unstable Angina

Francesco Cipollone, MD; Antonina Ganci, MD; Anita Greco, PhD; Maria Rosaria Panara, PhD; Massimo Pasquale, MD; Domenico Di Gregorio, MD; Ettore Porreca, MD; Andrea Mezzetti, MD; Franco Cuccurullo, MD; Paola Patrignani, PhD

From the Department of Medicine and Aging (F. Cipollone, A. Ganci, A. Greco, M.R.P., E.P., A.M., F. Cuccurullo, P.P.) and the Center for the Prevention of Atherosclerosis (F. Cipollone, A.M., F. Cuccurullo), University of Chieti "G. D’Annunzio" School of Medicine, Chieti; and the Divisions of Cardiology, "S.S. Annunziata" Hospital, Chieti (M.P.), and "F. Renzetti" Hospital, Lanciano (D.D.G.), Italy.

Correspondence to Francesco Cipollone, MD, Centro per la Prevenzione dell’Aterosclerosi, Università degli Studi "G. D’Annunzio," Via Pescara 66, 66013 Chieti, Italy. E-mail fcipollone{at}unich.it

Background— The evidence that inflammation plays a pivotal role in the pathophysiology of acute coronary syndromes prompted us to investigate the effects of glucocorticoid treatment on leukotriene (LT) C₄ and thromboxane (TX) A₂ biosynthesis in unstable angina.

Methods and Results— Urinary LTE₄ and 11-dehydro-TXB₂ were significantly higher in 12 patients with unstable angina than in 12 patients with stable angina and 12 patients with nonischemic chest pain. Furthermore, we randomized the unstable angina patients to receive intravenous 6-methylprednisolone (6-MP; 1 mg/kg BID for 2 days) or matching placebo and collected 12 consecutive 6-hour urine samples before and during the infusions. LTE₄ excretion showed a time-dependent decrease in the 6-MP group but did not decrease during placebo. Furthermore, during myocardial ischemia, LTE₄ was significantly higher before 6-MP infusion than during steroid therapy. In contrast, 11-dehydro-TXB₂ did not differ significantly during 6-MP versus placebo. Myocardial ischemia elicited by stress test in the stable angina patients was not accompanied by any change in LTE₄ and 11-dehydro-TXB₂, thus ruling out a role of ischemia per se in the induction of increased eicosanoid production.

Conclusions— Increased production of vasoactive LT and TX may occur in unstable angina despite conventional antithrombotic and antianginal treatment. Glucocorticoids can suppress LTC₄ biosynthesis in the short term and may provide an interesting tool to explore the pathophysiological significance of inflammatory cell activation in this setting.

Key Words: angina • inflammation • prostaglandins • leukocytes • platelets

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