Inflammation/inflammatory processes

Glucocorticoids have been shown to inhibit gene transcription of other proteins involved in the inflammatory process, including the key inflammation mediators called cytokines (IL-1, IL3—6, IL8, GM-CSF, TNFa) (10,58,63—65). Steroids have been also shown to suppress the formation of cytokine receptors (10) dexamethasone, in particular, downregulates gene transcription of angiotensin II type 2 receptors (66). 

These steioids aie capable of preventing or suppressing the development of the sweUing, redness, local heat, and tenderness which characterize inflammation. They inhibit not only the acute symptoms of the inflammatory process, such as edema, fibrin deposition, and capillary dilatation, but also the chronic manifestations. There is evidence that glucocorticoids induce the synthesis of a protein that inhibits phosphoHpase A 2 (60), diminishing the release of arachidonic acid from phosphoHpids (Fig. 2), thereby reducing chemotaxis and inflammation. 

Acute phase reactants (e.g., C-reactive protein) are proteins that increase during inflammation and are deposited in damaged tissues. They were first discovered in the serum, but are now known to be involved in inflammatory processes in the brain (e.g., found in the brain of Alzheimer patients and associated with amyloid plaques). 

Severe acute and chronic allergic and inflammatory processes, keratitis, allergic corneal marginal ulcers, herpes zoster of the eye, iritis, iridocyclitis, chorioretinitis, diffuse posterior uveitis, optic neuritis, sympathetic ophthalmia, anterior segment inflammation... 

In persistent asthma, inhaled corticosteroids provide the most comprehensive control of the inflammatory process and are the cornerstone of therapy.2 Inhaled corticosteroids are more effective than cromolyn, leukotriene modifiers, nedocromil, and theophylline in reducing markers of inflammation and AHR, improving lung function, and preventing emergency department visits and hospitalizations due to asthma exacerbations.2,25 The primary... 

Corticosteroids have potent anti-inflammatory properties and are used in active IBD to rapidly suppress inflammation. Corticosteroids have favorable effects in modulating several cell types involved in the inflammatory process.20,21 They may be administered systemically or delivered locally to the site of action by altering the drug formulation (Table 16-2). Because these drugs usually improve symptoms and disease severity rapidly, they should be restricted to short-term management of active disease. Long-term use of systemic corticosteroids is... 

Chronic pancreatitis is an inflammatory process that occurs over a long period of time. The inflammation damages the enzyme-producing cells in the pancreas and can also disrupt or destroy the endocrine function of the pancreas by causing diffuse... 

Inflammation is a common pathway in soft-tissue injury of musculoskeletal disorders. Inflammatory processes lead to two outcomes swelling and pain. Inflammatory processes... 

The key factor in the development of sepsis is inflammation. Inflammation is intended to be a local and contained response to infection or injury. Infection or injury is controlled through pro- and anti-inflammatory mediators. Pro-inflammatory mediators facilitate clearance of the injuring stimulus, promote resolution of injury, and are involved in processing of damaged tissue.1,13-16 In order to control the intensity and duration of the inflammatory response, antiinflammatory mediators are released that act to regulate pro-inflammatory mediators.15-16 The balance between pro- and anti-inflammatory mediators localizes infection/injury of host tissue.13-16 However, systemic responses ensue when equilibrium in the inflammatory process is lost. 

The inflammatory process in sepsis is linked to the coagulation system. Pro-inflammatory mediators maybe procoagulant and antifibrinolytic, whereas anti-inflammatory mediators may be fibrinolytic. A key factor in the inflammation of sepsis is activated protein C, which enhances fibrinolysis and inhibits inflammation. Protein C levels are decreased in septic patients. 

As discussed in the previous section, long-standing inflammation may result in accumulation of iron in the reticuloendothelial system. In HIV-1 infection, a good example of a prolonged inflammatory process, such an excessive deposition of iron has been documented, and it may be responsible for an enhanced risk of certain infections (Boelaert etal., 1996). For instance, two studies reported an increased risk of Mycobacterium avium infection when such an excess of iron was present, as histologically documented (A1 Khafaie et ah, 1997 De Monye et ah, 1999). 

At the cellular level, eosinophils, mast cells, alveolar macrophages, lymphocytes and neutrophils recruited to the airways of asthmatics produce a variety of inflammatory mediators, such as histamine, kinins, neuropeptides, and leukotrienes, which lead to airway smooth muscle constriction and obstruction of airflow, and the perpetuation of airway inflammation [20, 21]. An understanding of the inflammatory processes and the molecular pathways of these mediators has led to the development and widespread use of several pharmacologic agents that mitigate airway inflammation and bronchoconstriction. 

Inflammatory processes play an important role in development of many pathologies. The participation of inflammatory cells in the development of cardiovascular disease and cancer has already been discussed above. Below, we will consider the other pathologies, in which inflammation plays important and even deciding role. 

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. 

Goals of treatment include resolution of acute inflammatory processes, resolution of attendant complications (e.g., fistulas, abscesses), alleviation of systemic manifestations (e.g., arthritis), maintenance of remission from acute inflammation, or surgical palliation or cure. 

A number of studies have also involved the use of microarrays as tools for the evaluation of mechanisms of immunotoxicology. For example, toxic effects of ricin,23 hexachlorobenzene,24 and nickel,25 revealed an unexpected role for inflammatory processes. These findings illustrate the value of microarray analysis in identifying inflammation as a mechanism involved in the toxicopathology following exposure to a particular compound and highlight the underestimated importance of inflammatory processes in immunotoxicity. 

This chapter presents specific information with regard to the effects of environmental and occupational exposure to arsenic on inflammatory processes, the immune system, and host defense. While the focus is on the in vivo and in vitro effects of arsenic on host immune responses (e.g., immunotoxicity and hypersensitivity) and their relationship to clinically observed manifestations of arsenic toxicity (e.g., inflammation and skin cancer), information on the potential mechanisms through which arsenic may exert its biological effects is also provided. 

Inflammation is the normal host response to infection or injury that mediates immune elimination of pathogens and tissue repair. Inflammatory processes include increased production of cytokines, chemokines, nitric oxide, and eicosanoids by the innate immune system in conjunction with altered leukocyte homing, all of which greatly impact acquired immunity. Aberrant inflammatory responses evoke both acute injury such... 

The third type of response to injury, which falls under the general heading of inflammation (suffix itis ), manifests itself in several complex ways. It involves extracellular processes and cells of the immune system. Inflammation is often part of the road to repair from injury, but the inflammatory process can, if extensive, be highly damaging. Inflammation can be acute or chronic in nature. Repair can occur by regeneration of cells, for example by enhanced growth of adjacent cells or it can occur by a process called fibrosis. Some examples of inflammatory responses and repair are brought out in Chapter 4. 

Phthalates are suspected of acting as endocrine disrupters also in humans, affecting male and female reproductive tract development. Exposure to PAEs in adult men has been associated with semen quality and alterations in sexual behavior [104], and with endometriosis and intrauterine inflammation (which is a risk factor for prematurity) in adult women [105, 106], as well as other effects. These studies suggest that DEHP may play a role in inducing the intrauterine inflammatory process. Besides the reproductive effects of PAEs, recent studies have also shown the genotoxicity of DEHP, DBP, and DiBP in human lymphocytes and mucosal cells [107,108]. 

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