Fibrosis is the production of excessive amounts of connective tissue, i.e., scar formation, in the course of reactive and reparative processes. Fibrosis develops as a consequence of various underlying diseases and presents a major diagnostically and therapeutically unsolved problem. In this review, we postulate that fibrosis is always a sequela of inflammatory processes and that the many different causes of fibrosis all channel into the same final stereotypical pathways. During the inflammatory phase, both innate and adaptive immune mechanisms are operative. This concept is exemplified by fibrotic diseases that develop as a consequence of tissue damage, primary inflammatory diseases, fibrotic alterations induced by foreign body implants, "spontaneous" fibrosis, and tumor-associated fibrotic changes.

Infliximab treatment was not effective in refractory inflammatory myopathies. In view of radiological and clinical worsening, and activation of the type I IFN system in several cases, infliximab is not an alternative treatment in patients with treatment-resistant myositis.

Abstract-Hallmarks of inflammation in various cardiovascular diseases, notably atherosclerosis, have been observed for a long time. However, evidence for an (auto)antigen-driven process at these sites of inflammation has come forward only recently. Heat shock proteins (HSPs) have been identified as playing either immunologically mediated disease promoting or protective roles. HSP60 has been shown to trigger innate and adaptive immune responses that initiate the earliest still reversible inflammatory stage of atherosclerosis. HSP60 is structurally highly conserved and abundantly expressed by prokaryotic and eukaryotic cells under stressful conditions. Beneficial protective immunity to microbial HSP60 acquired by infection or vaccination and bona fide autoimmunity to biochemically altered autologous HSP60 is present in all humans. In vitro and in vivo experiments have demonstrated that classical atherosclerosis risk factors can act as endothelial stressors that provoke the simultaneous expression of adhesion molecules and of HSP60 in mitochondria, in cytoplasm, and on the cell surface, where it acts as a "danger signal" for cellular and humoral immune reactions. Hence, protective, preexisting anti-HSP60 immunity may have to be "paid for" by harmful (auto)immune cross-reactive attack on arterial endothelial cells maltreated by atherosclerosis risk factors. These experimentally and clinically proven findings are the basis for the autoimmune concept of atherosclerosis. (Arterioscler Thromb Vasc Biol. 2011;31:960-968.)Key Words: atherosclerosis Ⅲ endothelium Ⅲ immune system Ⅲ risk factors Ⅲ stress Ⅲ heat shock protein T ypical cellular hallmarks of chronic inflammation and infections, notably infiltration by mononuclear cells, are also present in the cardiovascular system, as has been known for more than 150 years. However, until quite recently, it was not clear whether these inflammatory immunologic processes are primary or secondary in nature. 1 One of the reasons for this uncertainty may have been the fact that most investigations in humans were conducted on surgical or autopsy specimens representing very advanced stages of cardiovascular disease (CVD) and thus did not provide information on the initial mechanisms triggering these processes. In complex situations, such as in atherosclerosis, it was also difficult to appreciate that different, clinically well-proven risk factors may provoke a similar, or even identical, pathophysiological outcome. The main thrust to resolve this dilemma was to delineate the array of nonspecific and specific humoral and cellular inflammatory reactions taking place within the afflicted vascular territories. The availability of animal models that, at least partly, mimic human CVD was of utmost importance for this progress. In recent decades, the aim has been to identify exogenous or autologous antigens that may induce the local cardiovascular immune reactions. Among the candidates for such antigens are infectious agents, such as Chlamydia pneumoniae, as well as autoantigens, such as b...

Atherosclerosis is a chronic, multifactorial disease that starts in youth, manifests clinically later in life, and can lead to myocardial infarction, stroke, claudication, and death. Although inflammatory processes have long been known to be involved in atherogenesis, interest in this subject has grown in the past 30-40 years. Animal experiments and human analyses of early atherosclerotic lesions have shown that the first pathogenic event in atherogenesis is the intimal infiltration of T cells at arterial branching points. These T cells recognize heat shock protein (HSP)60, which is expressed together with adhesion molecules by endothelial cells in response to classic risk factors for atherosclerosis. Although these HSP60-reactive T cells initiate atherosclerosis, antibodies to HSP60 accelerate and perpetuate the disease. All healthy humans develop cellular and humoral immunity against microbial HSP60 by infection or vaccination. Given that prokaryotic (bacterial) and eukaryotic (for instance, human) HSP60 display substantial sequence homology, atherosclerosis might be the price we pay for this protective immunity, if risk factors stress the vascular endothelial cells beyond physiological conditions.