Modulation of aspirin-insensitive eicosanoid biosynthesis by 6-methylprednisolone in unstable angina.
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.


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.
Cipollone
Francesco
F
Department of Medicine and Aging, University of Chieti G. D'Annunzio School of Medicine, Chieti, Italy. fcipollone@unich.it
Ganci
Antonina
A
Greco
Anita
A
Panara
Maria Rosaria
MR
Pasquale
Massimo
M
Di Gregorio
Domenico
D
Porreca
Ettore
E
Mezzetti
Andrea
A
Cuccurullo
Franco
F
Patrignani
Paola
P
D000328:Adult; D000789:Angina, Unstable / Q000378:metabolism / Q000652:urine*; D001241:Aspirin / Q000494:pharmacology; D001792:Blood Platelets / Q000187:drug effects / Q000201:enzymology; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004311:Double-Blind Method; D015777:Eicosanoids / Q000096:biosynthesis / Q000652:urine*; D005260:Female; D005938:Glucocorticoids / Q000494:pharmacology*; D006801:Humans; D017999:Leukotriene E4 / Q000652:urine; D008297:Male; D008775:Methylprednisolone / Q000494:pharmacology*; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000209:etiology; D013929:Thromboxane B2 / Q000031:analogs & derivatives* / Q000652:urine
D016861:Cyclooxygenase Inhibitors; D015777:Eicosanoids; D005938:Glucocorticoids; D013929:Thromboxane B2; C049235:11-dehydro-thromboxane B2; D017999:Leukotriene E4; D001241:Aspirin; D008775:Methylprednisolone