Atherosclerosis 206 (2009) 581–587 Contents lists available at ScienceDirect Atherosclerosis journal homepage: www.elsevier.com/locate/atherosclerosis Coronary sinus concentrations of interleukin 6 and its soluble receptors are affected by reperfusion and may portend complications in patients with myocardial infarction Karol A. Kaminski a,∗ , Marcin Kozuch b , Tomasz Bonda a , Izabela Wojtkowska c , Anna Kozieradzka a , Slawomir Dobrzycki b , Pawel Kralisz b , Konrad Nowak b , Przemyslaw Prokopczuk b , Maria M. Winnicka d , Wlodzimierz J. Musial a a Medical University of Bialystok, Department of Cardiology, Bialystok, Poland b Medical University of Bialystok, Department of Invasive Cardiology, Bialystok, Poland c National Institute of Cardiology, Intensive Cardiac Care Unit, Warsaw, Poland d Medical University of Bialystok, Department of General and Experimental Pathology, Bialystok, Poland article info Article history: Received 17 December 2008 Received in revised form 23 March 2009 Accepted 23 March 2009 Available online 5 April 2009 Keywords: Myocardial infarction Reperfusion Interleukin 6 IL-6 soluble receptors abstract Interleukin 6 (IL-6) is a pleiotropic cytokine involved in both inflammatory reaction and myocardial response to stress. Its effects largely depend on the concentration of the soluble receptors (sIL-6R and sgp130). We investigated the production of IL-6, sIL-6R and sgp130 by the heart during ischemia and reperfusion. Methods: The levels of IL-6 were determined in blood of 34 patients with first myocardial infarction (STEMI), left anterior descending (LAD) artery occlusion, otherwise normal coronaries, without significant co-morbidities and 16 comparable subjects with stable ischemic heart disease and lesion in LAD. Blood samples from coronary sinus (CS) and aorta (Ao) were drawn before percutaneous interven- tion (PCI), immediately after and at the end of the procedure. Venous blood from 30 healthy volunteers served as control. Results: STEMI patients presented high IL-6 concentrations that increased further after reperfusion when its levels in CS became significantly higher than in Ao. In both groups prior to the PCI there were significantly higher concentrations of sIL-6R in Ao than in CS. This difference disappeared immediately after reperfusion. STEMI patients who experienced cardiovascular complications had higher IL-6 concentration and higher transcardiac sIL-6R gradient than patients with event-free hospitalisation. This association was confirmed in multivariate logistic regression analysis. Myocardial infarction increases concentration of IL-6 that is further elevated by reperfusion. A tran- scardiac gradient of sIL-6R during ischemia may indicate that large amounts of soluble IL-6 receptors are bound to the infarcted heart and thus affect signal transduction. IL-6 and initial sIL-6R gradient may portend complications in STEMI patients. © 2009 Elsevier Ireland Ltd. All rights reserved. 1. Introduction Myocardial infarction is a major healthcare problem. Despite sig- nificant progress utilizing early reperfusion therapy it remains one of the leading causes of death and disability in the developed coun- tries [1]. Reducing reperfusion injury could significantly reduce the mortality rate associated with myocardial infarction [2]. Among the many important factors involved in the inflammatory reaction incited by reperfusion, interleukin 6 appears to be the key player [2]. ∗ Corresponding author at: Medical University of Bialystok, Department of Car- diology, ul. Sklodowskiej 24a, Bialystok, PL 15-276, Poland. Tel.: +48 857468656; fax: +48 857468604. E-mail address: fizklin@wp.pl (K.A. Kaminski). Interleukin 6 (IL-6) is a pleiotropic cytokine involved in vari- ous, often apparently contradictory processes. It is considered to be one of the most important elements of the inflammatory reac- tion [3], but simultaneously it may have anti-inflammatory effects by limiting expression of TNF and enhancing secretion of IL-10 [3,4]. Increased IL-6 is associated with a poor prognosis in patients with myocardial infarction or heart failure [5]. On the other hand it is of vital for benefit for effects of ischemic preconditioning [6] and limits atherosclerosis in experimental models [4]. These equiv- ocal findings may be explained by the interplay of IL-6 with its two receptors (IL-6R or gp80 and gp130). Both gp80 and gp130 can be expressed on the cell membrane or in functional soluble forms (sgp80 or sIL-6R and sgp130) that may bind circulating IL-6 [7]. The IL-6–sIL-6R complexes may affect cells that do not express specific IL-6 receptor (IL-6R) and only present ubiquitous gp130. Therefore, 0021-9150/$ – see front matter © 2009 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.atherosclerosis.2009.03.033