PubMed · 15433419
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J L MILLER. 1950. Poikilodermatomyositis.. https://pubmed.ncbi.nlm.nih.gov/15433419/
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The introduction of TNF-alpha inhibitors in the treatment of rheumatoid arthritis and several other diseases meant a major progress in the management and to the understanding of these chronic inflammatory diseases. In this article, the evidence of the role of TNF-alpha and for TNF-alpha inhibitors in systemic vasculitides and connective tissue diseases is reviewed. TNF-alpha is expressed in inflammatory lesions. TNF-alpha acts as a proinflammatory cytokine in most disease processes analyzed so far, but it might have anti-inflammatory properties under certain conditions as well, e.g. with respect to B-cell regulation in systemic lupus erythematosus. It is not clear to what extent such aspects will be important in the treatment of connective tissue diseases and systemic vasculitides with TNF-alpha inhibitors. So far, most case reports and case series have suggested favourable results with TNF-alpha inhibitor therapy in systemic lupus erythematosus, dermato- and polymyositis, giant cell arteritis, Churg-Strauss syndrome, Wegener's granulomatosis and microscopic polyangiitis. Results of randomized, placebo-controlled trials are awaited for several connective tissue diseases and systemic vasculitides. One randomized, placebo-controlled trial has found no efficacy of infliximab treatment in primary Sjögren's syndrome recently.
The endothelium is now considered a real endocrine-paracrine organ, important not only as a structural barrier between the circulation and surrounding tissue, but also because it plays an essential role for local hemodynamics, releasing substances that modulate the vascular calibre and blood cell activation. Here, after a brief but detailed analysis of the importance of the endothelium in vascular homeostasis, in the control of coagulation and in the relations with the different blood cells, we will explain the concept of endothelial dysfunction (altered NO release) and activation (amplified adhesion molecule expression) in inflammatory, connective tissue and post-trasplantation diseases. Furthermore, this review will focus on the activity of prostacyclin and synthetic analogs, especially their ability to interact with the vasodilatation system and their role in modulating cell interaction by surface adhesion molecule expression, cytokines and growth factors release as well as gene transcription factors. Finally, we will consider the therapeutic role of prostacyclin analogs in the prevention and treatment of connective tissue diseases.