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CLINICAL STUDY: MYOCARDIAL ISCHEMIA

Increased production of inflammatory cytokines in patients with silent myocardial ischemia

Antonino Mazzone, MD^*,*, Chiara Cusa, MD^*, Iolanda Mazzucchelli, BSc^*, Monia Vezzoli, MD^*, Elena Ottini, MD^*, Roberta Pacifici, BSc, Piergiorgio Zuccaro, MD and Colomba Falcone, MD

^* Department of Internal Medicine, Legnano Hospital, Milan Italy
Clinical Biochemistry Department, National Institute of Health, Rome Italy
Department of Cardiology, IRCCS S. Matteo Hospital, Pavia, Italy

Manuscript received March 20, 2001; revised manuscript received August 7, 2001, accepted August 27, 2001.

^* Reprint requests and correspondence: Dr. Antonino Mazzone, Chief of Internal Medicine and Oncology, Hospital of Legnano, Via Candiani 2, 20025 Legnano, Milano, Italy
medicina2legnano{at}ao-legna.no

OBJECTIVES

The aim of the study was to examine the inflammatory cytokines in patients with myocardial ischemia to evaluate whether silent ischemia patients exibit any particular cytokine pattern.

BACKGROUND

Silent myocardial ischemia is frequently observed in patients with coronary artery disease. Various endogenous mechanisms control a patient’s perceived intensity of pain. Among them, the inflammatory process and the related cytokine production are known to modulate the threshold for activating the primary afferent nociceptors.

METHODS

Seventy-eight patients with reproducible exercise-induced myocardial ischemia were studied: 34 symptomatic patients, with rest and/or stress angina; 44 asymptomatic patients, with no symptoms during daily life activities or during positive exercise stress test. Venous blood samples were taken from all patients to evaluate the expression of CD11b receptors both on neutrophils and monocytes. Frozen plasma samples (at –80°C) were used to quantify the anti-inflammatory (interleukin-4 and -10, transforming growth factor-ß) and the proinflammatory cytokines (tumor necrosis factor-, interferon-, interleukin-1ß and -6).

RESULTS

In asymptomatic patients lower CD11b receptor expression and higher concentration of anti-inflammatory cytokines were observed. Proinflammatory cytokine production was similar in the two groups.

CONCLUSIONS

The data suggest that an "anti-inflammatory pattern" of cytokine production correlates with silent ischemia and that the immune and inflammatory system activation may be crucial for angina symptoms.

Abbreviations and Acronyms   CAD = coronary artery disease   CGRP = calcitonin gene-related peptide   ECG = electrocardiogram or electrocardiographic   IFN- = interferon-gamma   IL = interleukin   MAb = monoclonal antibodies   MESF = molecules of equivalent soluble fluorescein   MI = myocardial infarction   NF-B = nuclear factor-B   PBR = peripheral benzodiazepine receptor   SP = substance P   TGF-ß = transforming growth factor-beta   TNF- = tumor necrosis factor-alpha

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