Inflammation, coagulation, vascular permeability and thrombosis

Ample evidence exists on the close link among the immune response, inflammation and coagulation [1, 2]. Proinflammatory cytokines such as interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-α) induce the expression of tissue factor (TF) the main initiator of blood coagulation [2]. TF activates the coagulation cascade generating thrombin which leads to the formation of fibrin clot from fibrinogen. At the cellular level, the coagulant mediators act on protease-activated receptors (PARs) inducing the expression of proinflammatory cytokines [3]. In turn, the two systems - coagulation and inflammation - activate each other, thus increasing the response. This self-refuelling loop may be amplified by the dysfunction of the major natural anticoagulant pathways (i.e. antithrombin, protein C system, and tissue factor pathway inhibitor) occurring in several inflammatory conditions [4]. Inflammation affects the coagulation system as observed in sepsis [5], rheumatoid arthritis [6, 7], autoimmune skin diseases [8, 9], inflammatory bowel diseases [10], and hypereosinophilic syndromes [11] which show an increased risk of thrombosis. Moreover, inflammatory mediators, acting synergistically with coagulation factors, may contribute to increase vascular permeability in conditions like urticaria and other cutaneous disorders [12, 13]. In this issue we will focus on several aspects of the complex interplay between inflammation and coagulation in different human diseases: sepsis (Chapter 1), rhematoid arthritis (Chapter 2), autoimmune and immune-mediated skin diseases (Chapter 3), urticaria and angioedema (Chapter 4), inflammatory bowel diseases (Chapter 5), and hypereosinophilic conditions (Chapter 6). The final aim is to identify new targets for therapies that can modify the dysregulation of coagulation and inflammation pathways, acting both locally, by preventing tissue damage and vascular hyperpermeability, and systemically, by reducing thrombotic risk