Inflammation/inflammatory processes initiation

There are a number of nonspecific laboratory tests that are useful to support the diagnosis of infection. The inflammatory process initiated by an infection sets up a complex of host responses. Activation of complements, such as C3a and C5a, initiates inflammation and sets off a cascade of changes and the subsequent release of mediators, all of which can be measured and monitored. Serum complement concentrations, particularly C3, usually are consumed as part of the host defense mechanism and subsequently are reduced during the early stages of an acute infectious process. Acute-phase reactants, such as the erythrocyte sedimentation rate (ESR) and the C-reactive protein concentration, are elevated in the presence of an inflammatory process but do not confirm the presence of infection because they are often elevated in noninfectious conditions, such as collagen-vascular diseases and arthritis. Large elevations in ESR are associated with infections such as endocarditis, osteomyelitis, and intraabdominal infections. ... 

The nasal passages are subject to inflammation from irritants, viral and bacterial infection, and allergens. The inflammatory process initiates a production of thin, watery mucus leading to rhinorrhea. In some infectious processes, the mucus later becomes thick and tenacious, frequently colored green or yellow, especially in bacterial infections. The turbinates swell and block the nasal passages, making inhalation through the nose difficult. 

Inflammation is characterized by the orderly occurrence of several processes initiation of the event by a foreign substance or physical injury, recruitment and chemoattraction of inflammatory cells, and activation of these cells to release inflammatory mediators capable of damaging or killing an invading microbe or tumor. In some instances, the inflammatory response is initiated by an otherwise harmless foreign material (e.g., pollen). Inflammation can also result from an autoimmune response to the host s own tissue, as occurs in rheumatoid arthritis. 

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). 

The acute inflammatory process is associated initially with increased HA levels, the result of the cytokines released by the polymorphonuclear leukocytes, the predominant cells of the acute inflammatory process. The erythema, swelling, and warmth of the acute process are followed later by the characteristic dry appearance and the formation of wrinkles. The precise mechanisms are unknown, but may relate to the differences between acute and chronic inflammatory cells and the attendant chemical mediators released by such cells. Alternatively, initiation of a wound healing response, with collagen deposition, may be a mechanism invoked for the premature aged appearance of the skin in chronic inflammation. 

Tumor necrosis factor (TNF), interleukin-1 (IL-1), and IL-6 are proinflamma-tory cytokines important in the initiation and continuance of inflaimnation. Activated T cells produce cytotoxins, which are directly toxic to tissues, and cytokines, which stimulate further activation of inflammatory processes and attract cells to areas of inflammation. Macrophages are stimulated to release prostaglandins and cytotoxins. 

As far as the inflammatory process concerns, the bulk of the data indicates that NO is pro-inflammatory. However, the conflicting notion that NO may be protective during an inflammatory insult also exists. For instance, leukocyte adhesion and infiltration, characteristic of the initial steps of inflammation, depends on the interaction of the leukocytes with the endothelial cell surface via glycoproteins (endothelial cell adhesion molecules, ECAM). NO modulates cytokine-induced ECAM expression in cultured endothelial cells in vitro by regulating the activation of NF-kB. Hence NO activity may result in this case as anti-inflammatory [50]. 

Inflammatory cells infiltrating postischemic tissue are considered to contribute to disability after cerebral ischemia [5,8,17]. Identification of factors involved in the selective recruitment and accumulation of inflammatory cells into ischemic brain tissue and the mechanisms behind the entry of leukocytes through the blood-brain barrier into sites of ischemia are not completely understood [5,8]. Locally produced proinflammatory cytokines such as TNF-a, IL-1 P, and IL-6 initiate the inflammatory process. TNF-a and IL-1 P mRNA elevate in the brain after experimental middle cerebral artery occlusion [5,51,81]. While, IL-1 p and TNF-a play a major role in promoting adhesion between endothelial cells and leukocytes, they are poor attractants for polymorphonuclear leukocytes and monocytes [7]. Astrocytes and endothelial cells can respond in vitro to such proinflammatory cytokines with enhanced expression of chemokines, which results in the influx of leukocytes to areas of inflammation [5,8,103]. 

The initial chapters introduce to the general knowledge necessary to understand flie inflammatory process and the role played of free radical and oxidative stress. The interplay between inflammatory molecules and cell signalling is also dealt with in depth. A second part is dedicated to nitric oxide, redox regulation and antioxidant function in inflammation. The final chapters are devoted to diseases where inflammation plays the dominant role septic shock, end-stage renal disease, neurodegenerative, ischemic and lung diseases. 

The causal relationship between inflammation, innate immunity, and cancer is now widely accepted. Normal inflammation is self-limiting because the production of proinflammatory cytokines is followed by that of anti-inflammatory cytokines. In tumors, the inflammatory process persists. Chronic inflammation seems to be due to persistence of the initiating factors or failure of mechanisms that are required to resolve the inflammatory response [139]. The strongest association of chronic inflammation with malignant diseases is in colon carcinogenesis in patients with inflammatory bowel diseases such as chronic ulcerative colitis and Crohn s disease. 

Chronic inflammation of the synovial tissue lining the joint capsule results in the proliferation of this tissue. The inflamed, proliferating synovium characteristic of rheumatoid arthritis is called parmus (Fig. 89-1). This pannus invades the cartilage and eventually the bone surface, producing erosions of bone and cartilage and leading to destruction of the joint. The factors that initiate the inflammatory process are unknown. 

The pathogenesis of prostate cancer reflects both hereditary and environmental components, and growing evidence suggests a role for chronic inflammation in prostate cancer [21, 22, 78], The exact mechanisms by which inflammatory processes contribute to the initiation and progression of prostate cancer remain... 

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