Rheumatoid Arthritis
Rheumatoid arthritis (RA) is a chronic and systemic musculoskeletal autoimmune disease, with extra-articular organ involvement, characterized by an imbalance in the neuroendocrine-immune (NEI) system.
- PDF / 299,635 Bytes
- 6 Pages / 504.57 x 720 pts Page_size
- 72 Downloads / 213 Views
Introduction to Rheumatoid Arthritis Rheumatoid arthritis (RA) is a chronic and systemic musculoskeletal autoimmune disease, with extra-articular organ involvement, characterized by an imbalance in the neuroendocrine-immune (NEI) system. The prevalence of RA is suggested to range from 0.5 to 1 % in the world population. In addition, women are more frequently affected. RA is characterized by a chronic inflammatory process of body joints, with a usual symmetrical, centripetal pattern (starting from peripheral, small joints, and gradually involving major joints). Joint inflammation leads to synovial hypertrophy and juxta-articular bone erosion. The phlogistic process manifests both locally (in joints) and systemically (affecting also lung, heart, kidney, and other organs and tissues), causing symptoms like fever, weight loss, and anorexia. Efforts to understand the pathophysiology of these manifestations identified a proinflammatory cytokine network as a leading factor in RA. Tumor necrosis factor α (TNFα) is a major inflammatory mediator in RA, and its isolation has
M. Meroni • E. Bernero • M. Cutolo (*) Research Laboratory and Academic Division of Clinical Rheumatology, Department of Internal Medicine, University of Genova, Viale Benedetto XV, 6, Genova 16132, Italy e-mail: [email protected]; [email protected]; [email protected]
formed the basis of early RA treatments. Other important proinflammatory cytokines include interleukins (ILs) like IL-1, IL-2, IL-6, and IL-17, transforming growth factors α and β, and interferon γ. It is known since the nineteenth century that pregnancy improves RA clinical manifestations, and since 1950, correlations between inflammation and steroid hormones, particularly cortisol and sex hormones, have been suggested [1, 2]. In addition, autoimmune diseases in general present a higher incidence in women in reproductive ages, when sex hormone levels are higher, even if advanced-age cases of autoimmune diseases are partially explained by altered peripheral metabolism of sex hormones [3]. Furthermore, by observing the circadian undulation of symptoms in autoimmune diseases, a link between circadian rhythms of the central nervous system, endocrine systems, and immunologically mediated phenomena becomes evident (Fig. 1) [4].
Pathophysiology of Rheumatoid Arthritis and Metabolic Alterations An integrated network of the nervous, endocrine, and immune systems is now termed as neuroendocrine-immune (NEI) concept. The NEI system is mainly constituted of the hypothalamic-pituitary-adrenal (HPA) axis, the hypothalamic-pituitary-gonadal axis, and other complex systems such as the vitamin D endocrine system.
E. Lammert, M. Zeeb (eds.), Metabolism of Human Diseases, DOI 10.1007/978-3-7091-0715-7_19, © Springer-Verlag Wien 2014
115
M. Meroni et al.
116
IL-6
Androstenedione [17β-HSD]
TNF-α IL-1 IL-6
A E Macrophage Articular cartilage
TNF-α IL-1 IL-6
[Aromatase] Synovial fluid
A
IgG Estrone
Estradiol
E B lymphocyte
Estrogens (E) Androgens (A)
Synovial inflammation
IL-2 INFγ
Data Loading...
