Introduction

Abstract

Atherosclerosis, and its complications cerebral and myocardial infarction and gangrene of the extremities, is the leading cause of death in industrialized societies. Large epidemiological studies have revealed the main risk factors associated with an increased risk for atherosclerotic disease to be smoking, hypertension, diabetes and dyslipidaemias. However, these classical risk factors explain only a part of the epidemiological features of atherosclerotic vascular disease. During the last two decades, immunological mechanisms have been increasingly implicated. Postulates for the involvement of innate and adaptive immunity with cellular as well as humoral components have met with considerable experimental support. It is now well recognized that atherosclerotic lesions contain activated, immunocompetent cells, including T cells reactive towards oxidized LDL lipoproteins, heat shock proteins and possibly also other autoantigens. Systemic humoral immune responses can also be detected against such antigens and have been correlated to disease progression in some prospective clinical studies. Immune complexes can appear both in the circulation and in the artery wall, where they can activate complement and thus cause tissue destruction. Immune mechanisms appear to be particularly active when plaques are activated and rupture and they may therefore cause acute coronary syndromes. At such occasions, acute phase reactants, immune cytokines and activated T cells can be detected in the systemic circulation in amounts that correlate to the clinical course of disease. In addition to autoantigens, microbes have been implicated as potential pathogenic factors in atherosclerosis in several recent studies. In particular, Chlamydia pneumoniae can be detected in plaques, can elicit antibody responses that are associated with ischaemic heart disease and has been reported to accelerate experimental atherosclerosis. Although still not completely understood, the possibility of a microbial pathogenic component in atherosclerosis is an exciting challenge for further research and could provide new opportunities for therapy and prevention. Recent research in several laboratories throughout the world have provided important new insights into immunopathogenic and infection mechanisms in atherosclerosis. The Journal of Internal Medicine sponsored a conference with leading investigators in this field in April 1999. The present volume contains state-of-the-art reviews on this controversial topic by the speakers at the conference. It is our hope that it will serve as an introduction and an overview of this important aspect of current research in internal medicine.