INTERLEUKIN-1 IN MYOCARDIUM AND CORONARY-ARTERIES OF PATIENTS WITH DILATED CARDIOMYOPATHY

Idiopathic dilated cardiomyopathy (DCM) is characterised by a severe d ysfunction of the heart muscle resulting in terminal heart failure. It s pathogenesis is believed to be multifactorial involving genetic pred isposition, viral infection and autoimmunity, but little is known in d etail, and there is no curative treatment except transplantation. Inte rleukin-1 (IL-1) mediates inflammatory responses to infection and inju ry. It can be produced by several widely-distributed cell types, inclu ding macrophages, and is thought to depress myocyte contractility by s timulating nitric oxide synthase, To investigate whether this pro-infl ammatory cytokine may be a pathogenic mediator in DCM, IL-1 beta mRNA and protein were evaluated in coronary arteries and myocardium from pa tients undergoing cardiac transplantation for DCM. IL-1 beta mRNA was detected by PCR of cDNA and northern blots of mRNA in coronary arterie s and myocardium from patients with DCM. By comparison, samples from p atients with ischaemic heart disease (MD) contained much less IL-1 bet a mRNA, In contrast, mRNA for other cytokines (TNF alpha, IL-6, IL-10, PDGFA) were similar in both pathologies. In DCM, IL-1 beta mRNA and p rotein were localised to infiltrating macrophages in interstitial regi ons between myocytes, some of the myocytes themselves, and endothelial cells of Vessels in the wall of the arteries. These results suggest t hat local production of the pro-inflammatory cytokine, IL-1 beta may p lay a part in the pathogenesis of DCM. (C) 1998 Academic Press Limited .