Pathogenetic significance of proinflammatory cytokines, nonspecific proteinases and their inhibitors for the risk of complications of acute myocardial infarction

Abstract

Purpose of this investigation was to evaluate the interrelationships of proinflammatory cytokines and nonspecific proteinases serum levels with the development of myocardial infarction (MI) complications. Methods. Eighty two patients with MI were studied. Prospective short-term study included patients with uncomplicated non-Q wave MI (n = 27), patients with Q-MI complicated by acute left ventricular insufficiency I—II Killip (n = 30), patients with Q-MI complicated by acute left ventricular insufficiency III—IV Killip (n = 17), non-survivors due to development of cardiogenic shock (n = 8) and age and gender matched healthy controls (n = 12). Serum levels of IL-1β, IL-6 and TNF-α had been evaluated by means of ELISA method, also were determine the elastase-like (ELA) and trypsine-like (TLA) activities and level of proteinase inhibitors (antitrypsin activity and acid-stable inhibitors). Blood samples had been drawn on admission to the hospital within 24 hours from the onset of symptoms, at 3d and 14th days of MI. Results. All cytokines levels were significantly elevated in MI patients in comparison to controls. Mean concentrations of IL-6 at baseline were higher among patients with MI complicated by acute left ventricular insufficiency than in group with uncomplicated MI (27.6 vs 16.0 pg/mL; p<0.001). The same was revealed in concentration of TNF-α (24.7 vs 19.6 pg/mL; p<0.01), while mean concentration of IL-1β did not differ significantly between these two groups. Non-survivors also showed significantly higher levels of IL-6, TNF-α, ELA and TLA and lower level of proteinase in hibitors than patients with uncomplicated MI. Activation of proteolytic enzyme activity developed together with changes level of proteinase inhibitors. In some cases level of elastase activity increases in 2—3 times. Conclusion: Increased levels of IL-6 and TNF-α, as well as nonspecific proteinases serum levels within 24 hours from the onset of MI are associated with the development of ALVF and poor prognosis and indicate participation of proteinase-inhibitory system in pathogenesis of MI. The data support the role of excessive cytokine-mediated inflammation in worsening of MI course and outcome.