Immunology of cardiovascular disease.

摘要

The writings of Russell Ross between the mid 70s and late nineties summarized the remarkable evolution of our thinking about the pathogenesis of atherosclerosis in the late part of the 20th century such that today we talk about the immunology of cardiovascular disease. We have gone from two independent disciplines to the recognition of a remarkable interdigitation of interests. In 1976, the main emphasis was on the response to (endothelial) injury as the main underlying pathogenic mechanism, and on the possible role of hyperlipidemia as the insult leading to endothelial damage [1]. By 1993, Ross emphasized the role of inflammatory processes triggered by endothelial and smooth muscle cell damage [2]. Six years later Ross re-defined atherosclerosis as an inflammatory disease [3]. During those two decades, significant progress had been made in the understanding of the components of the vascular inflammatory reaction. Activated macrophages and T lymphocytes were well represented in atheromatous lesions at all stages of evolution [4-6]. Their contribution to inflammation and tissue damage through mediator release had been accepted as an essential step in the evolution of atherosclerosis. The phenotype of the infiltrating lymphocytes, however, does not fit into the classical Th1-Th2 dichotomy, because the majority seems to produce both interferon-gamma and IL-4, although interferon-gamma appears to be the predominant cytokine produced [7]. In recent years our knowledge about the complexity of regulatory and activation circuits mediated by T lymphocytes and their products has increased exponentially and animal studies suggest that the role of T cells in atherosclerosis is rather complex, as summarized in this issue by Andersson et al. But from the very beginning it was obvious that the involvement of the immune system was not limited to T lymphocyte-mediated inflammation, because immunoglobulins, and late complement components were also detectable in atheromatous lesions and their role the object of speculation [8-10].