Inflammatory response mediator

Fig. 14.1. The Thl/Th2 balance is central to the regulation of normal wound repair. Tissue injury results in the initiation of an inflammatory response, mediated by a variety of cells and their by-products. Immune cells are recruited and cross-regulate the Thl/ Th2 balance that occurs in response to the cytokine environment. This balance is in turn cross-regulated by the chemokine/chemokine-receptor expression profile, which functions to amplify the inflammatory process. Cells residing in the injured tissue release profibrotic mediators, which promote fibroblast activation, proliferation, and differentiation to the myofibroblast phenotype. Myofibroblasts produce collagen to repair damaged tissue, which is an event that is favored by the inhibition of MMP activity. The Thl/Th2 balance is central to whether a normal or aberrant wound-repair process is established A Thl environment promotes normal tissue resolution (fibrinolysis), whereas a Th2 environment maintains the progression of fibrotic disease (excessive collagen deposition).

Oxidized LDL provokes an inflammatory response mediated by a number of chemoattractants and cytokines (e.g., monocyte colony-stimulating factor, intercellular adhesion molecule, platelet-derived growth factor, transforming growth factors, interleukin-1, interleukin-6). 

The molecular mechanism by which IFN-/1 induces its therapeutic effect is complex and not fully understood. It is believed that the pathology of multiple sclerosis is linked to the activation and proliferation of T lymphocytes specific for epitopes found on specific myelin antigens. Upon migration to the brain, these lymphocytes trigger an inflammatory response mediated by the production of pro-inflammatory cytokines, most notably IFN-y, IL-1, IL-2 and TNF-a. The inflammatory response, in addition to other elements of immunity (e.g. antibodies and... 

Salmonella in the gut lumen can induce a host inflammatory response mediated by several proteins excreted from the bacterial cytoplasm through Salmonella TTSS-1. These virulence factors may play a role in the influx of neutrophils into the intestine and the resulting inflammation that leads to diarrhea and other symptoms (Norris et al., 1998) (Fig. 5.1). Inflammation is an important component of innate immunity that plays a role in recruiting host immune cells to damaged tissue or invading microbes. Interaction with components of the innate immune system initiates a cascade of events that can lead to elimination of the microbe (Singh et al., 2009). 

Dalakas MC (1999) Advances in chronic urflammatory demyelinating polyneuropathy Disease variants and inflammatory response mediators and modifiers. CuiT Opin Neurol 12 403 09. 

Nedocromil sodium was developed by changing the furan ring of khellin to a piperidinone ring (Fig. 44.32). In vitro, nedocromil sodium inhibits the release of inflammatory response mediators from a variety of cells, including neutrophils, mast cells, macrophages, and platelets. Inhaled nedocromil sodium is poorly absorbed into the systemic circulation, with approximately 3% of an inhaled dose excreted in the urine during the first 6 hours after administration. Only 2% of orally dosed nedocromil sodium is bioavailable, 89% of which is protein bound. When administered IV, nedocromil sodium is not metabolized and is excreted unchanged in the bile and the urine. Nedocromil sodium is available in aerosol canisters for oral inhalation via a mouthpiece. 

Remirez, D., Ledon, N., and Gonzalez, R. (2002). Role of histamine in the inhibitory effects of phycocyanin in experimental models of allergic inflammatory response. Mediators Inflamm. 11, 81-85. 

Pleurodesis is defined as the adherence of the visceral and parietal pleural surfaces with obliteration of their margins. Several agents are used as sclerotic agents to produce pleurodesis in patients with malignant pleural effusions, pneumothorax, and in rare cases of intractable pleural effusion (47). It appears that an acute inflammatory response mediated via interleukin-8 and MCP-1 is essential for the initiation of sclerosis (48). When talc was insufflated into the pleural space of 13 consecutive patients with spontaneous pneumothorax and eight patients with malignant pleural effusion, there was a rapid accumulation of neutrophils followed by mononuclear cells (49). The neutrophil influx correlated with the level of IL-8 in the pleural fluid however, the mononuclear cells did not appear to correlate with the level of MCP-1. 

Asbestos particles therefore initiate an inflammatory response mediated via the pleural mesothelial cell release of chemokines in the pleural space (55-57). Chemokines play an important role in the pathogenesis of asbestos-induced pleural effusions. Typically, patients with asbestos-induced pleural effusions have recurring episodes of fluid formation which may resolve spontaneously. These repeated episodes are presumed to be due to new asbestos fibers activating pleural mesothelial cells. Whether chemokines such as IL-8 that are present in such high quantities in asbestos-induced pleural disease play any role in mesothelial cell transformation into mesothelioma remains unclear. The association of asbestosis and mesothelioma has been well described, but the origin and pathobiology of the disease remain clouded. 

LTC may enhance the survival of mice partially via physiological changes such as induction of hypoxia (217). However, LTC mediates a number of physiological changes, including inflammatory responses and cardiovascular changes, that may also be important. 

Human bodies are constantly exposed to a plethora of bacteria, viruses, and other inflammatory substances. To combat these infections and toxic agents, the body has developed a carefully regulated inflammatory response system. Part of that response is the orderly migration of leukocytes to sites of inflammation. Leukocytes literally roll along the vascular wall and into the tissue site of inflammation. This rolling movement is mediated by reversible adhesive interactions between the leukocytes and the vascular surface. 

While the findings in mice are of interest, it is important to note that there are four known mammalian adenosine receptors and that the pattern of adenosine receptor expression on mast cells (as well as other immime cells and/or structural cells), and the regulation of their expression by such cells (e.g., during inflammatory responses), which can represent major determinants of adenosine responses, vary substantially among species [70-72]. For example, it is thought that adenosine-induced broncho-constriction is mediated by adenosine A1 and A2B receptors in rats and mice, A3 receptors in rats, guinea-pigs and mice, and A2B receptors in humans [72]. 

When looking at macrophage function in mediating inflammatory responses, several groups have shown either a marked induction or suppression of cytokine and... 

Inflammation is a non-specific reaction which can be induced by a variety of agents apart fiom microorganisms. Lymphokines and derivatives of arachidonic acid, including prostaglandins, leukotrienes and thromboxanes are probable mediators of the inflammatory response. The release of vasoactive amines such as histamine and serotonin (5-hydroxytryptamine) firm activated or damaged cells also contribute to inflammation. 

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