Vascular inflammatory processes

Neurological involvement in Behcet s disease may be subclassified into two major forms a vascular-inflammatory process with focal or multifocal parenchymal involvement and a cerebral venous sinus thrombosis with intracranial hypertension. The vasculitis and meningitis may affect cerebral arteries, particularly in the posterior circulation, to cause ischemic stroke and possibly intracranial hemorrhage (Farah et al. 1998 Krespi et al 2001 Siva et al. 2004 Borhani Haghighi et al. 2005). 

In contrast to previous claims, even low-dose interferon beta-lb can produce severe local reactions and cutaneous necrosis, with no recurrence after interferon alfa injection and expected better tolerance to interferon beta-la (52-55). The mechanisms of interferon beta-induced local skin reaction might involve a local vascular inflammatory process or platelet-dependent thrombosis, but positive intracutaneous tests to interferon beta have also been found (56). 

As with UC, the immune activation seen in CD involves the release of many proinflammatory cytokines. Cytokines thought to play major roles in CD are derived from T-helper type 1 cells and include interferon-y, TNF-a, and IL-1, IL-6, and IL-12. TNF-a is a major contributor to the inflammatory process seen in CD. Its physiologic effects include activation of macrophages, procoagulant effects in the vascular endothelium, and increases in production of matrix metallo-proteinases in mucosal cells.9,15 Excessive production of both... 

Our understanding of atherosclerosis as an inflammatory process has made great strides in the past decade, and it is clear from animal studies as well as clinical data that chemokines play an important role in atherosclerotic vascular... 

Deposition of urate crystals in synovial fluid results in an inflammatory process involving chemical mediators that cause vasodilation, increased vascular permeability, complement activation, and chemotactic activity for polymorphonuclear leukocytes. Phagocytosis of urate crystals by leukocytes results in rapid lysis of cells and a discharge of proteolytic enzymes into the cytoplasm. The ensuing inflammatory reaction is associated with intense joint pain, erythema, warmth, and swelling. 

Nearly all cells express kinin receptors that mediate the activities of both bradykinin and kallidin. The activation of these G-protein coupled receptors causes relaxation of venular smooth muscle and hypotension, increased vascular permeability, contraction of smooth muscle of the gut and airway leading to increased airway resistance, stimulation of sensory neurons, alteration of ion secretion of epithelial cells, production of nitric oxide, release of cytokines from leukocytes, and the production of eicosanoids from various cell types [11,12]. Because of this broad spectrum of activity, kinins have been implicated as an important mediator in many pathophysiologies including pain, sepsis, asthma, rheumatoid arthritis, pancreatitis, and a wide variety of other inflammatory diseases. Moreover, a recent report demonstrated that bradykinin B2 receptors on the surface of human fibroblasts were upregulated three-fold beyond normal in patients with Alzheimer s disease, implicating bradykinin as a participant in the peripheral inflammatory processes associated with that disease [13]. 

The transfection data summarized in Fig. 13 were obtained with primary human umbilical artery endothelial cells (HUAEC). Vascular endothelial cells, acting as an interface between circulating blood and tissues, are known to be involved in inflammatory processes, in atherosclerosis and angiogenesis, and represent a remarkable challenge as a gene therapy target. Their therapy with nonviral vectors... 

Vascular intervention results in cellular injury and the release of several mediators of thrombotic and inflammatory processes. Endothelial cell injury results in luminal thrombosis, inflammatory cell infiltration, cellular proliferation, and... 

There are multicellular interactions that are important in inflammatory processes and in vascular remodeling. Activated platelets induce endothelial cells to secrete chemokines and to express adhesion molecules, indicating that platelets could initiate an inflammatory (Table I) response of the vessel wall. Activated platelets promote leukocyte binding to inflamed or atherosclerotic lesions (27,28). Cell adhesion molecules (CAMs) are responsible for leukocyte-endothelium interactions. It plays a crucial role in inflammation and atherogenesis. Vascular CAM-1 (VCAM-I)and intracellular CAM-1 (ICAM-I) promote monocyte recruitment to sites of injury and constitute a critical step in inflammation and in atherosclerotic plaque development. TSP-1, a matricellular protein released in abundance from activated platelets and accumulated in sites of vascular injury, induces the expression of VCAM-1 and ICAM-1 on endothelium and significantly increases the monocyte attachment (29). 

COX-2 is induced by inflammatory processes and produces prostaglandins that sensitize nociceptors, evoke fever, and promote inflammation by causing vasodilation and an increase in vascular permeability. However, in some organs, COX-2 is also expressed con-stitutively (kidney, vascular endothelium, uterus, and CNS). 

---