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Cyclosporine demonstrates immunosuppressive activity by inhibiting the first phase of T-cell activation. It also inhibits release of inflammatory mediators from mast cells, basophils, and polymorphonuclear cells. It is used in the treatment of both cutaneous and arthritis manifestations of severe psoriasis. The usual dose is between 2.5 and 5 mg/kg/day given in two divided doses. Adverse effects include nephrotoxicity, hypertension, hypomagnesemia, hyperkalemia, alterations in liver function tests, elevations of serum lipids, GI intolerance, paresthesias, hypertrichosis, and gingival hyperplasia. Cumulative treatment for more than 2 years may increase the risk of malignancy, including skin cancers and lymphoproliferative disorders. 

The major prophylactic effect of cromolyn is centered on inhibition of the degranulation of pulmonary mast cells causing a reduction in histamine release, reduced leukotriene production, and inhibition of release of inflammatory mediators from several cell types. 

An effective immunosuppressive agent that inhibits the first phase of T-cell activation, cyclosporine is used in the treatment of both cutaneous and arthritic manifestations of severe psoriasis. It also inhibits the release of inflammatory mediators from mast cells, basophils, and polymorphonuclear cells. ... 

Theophylline also inhibits synthesis and secretion of inflammatory mediators from numerous cell types, including mast cells and basophils. This effect of theophylline is likely due to PDF inhibition and can be mimicked in large part with drugs that selectively inhibit PDF4 isozyme. At therapeutic concentrations, the antiinflammatory effect of theophylline may be more relevant to the drug s therapeutic actions than direct bronchodilation, but this remains unproven. 

This variant of the Kounis syndrome includes patients of any age, with normal coronary arteries, without predisposing factors for coronary artery disease, in whom the acute release of inflammatory mediators from mast cells can cause either sudden coronary artery narrowing, without increases in cardiac enzymes or troponins, or coronary artery spasm that progresses to acute myocardial infarction, with raised cardiac enzymes and troponins [93 ]. 

Elevation of cycHc AMP levels is also known to inhibit the release of inflammatory and contractile mediators from mast cells (42). The good clinical efficacy of P2" goiAsts may be related to this action because some members of this class of dmgs inhibit mediator release at the same concentrations at which they relax smooth muscle (43). In contrast to their effectiveness against immediate bronchoconstriction, P2" gonists do not inhibit the late asthmatic... 

Inflammation. Figure 1 Sequence of events in the recruitment of leukocytes in postcapillary venules adjacent to injured tissue. At the site of lesion, diverse reactive substances stimulate the endothelium to produce inflammatory cytokines, chemoattractants and other inflammatory mediators. The cytokine-activated endothelium expresses adhesion molecules that lead to the low affinity interactions between leukocytes and endothelium, which is mediated by selectins and described as rolling. Subsequently integrins mediate the firm adhesion of leukocytes, which allows emigration of the cells from venules into the interstitial compartment. Activated mast cells, PMNs and macrophages secrete cytokines (TNFa), lipid mediators (LTB4) and other inflammatory players (histamine, NO). 

The mast cell stabilizers currently for ophthalmic use are nedocromil and pemirolast. These drugp are used for the prevention of eye itching caused by allergic conjunctivitis. The mast cell stabilizers act by inhibiting the antigen-induced release of inflammatory mediators (eg, histamine) from human mast cells. 

Mast cells express high-affinity IgE Fc receptors (FceRI) on their surface, contain cytoplasmic granules which are major sources of histamine and other inflammatory mediators, and are activated to release and generate these mediators by IgE-dependent and non-IgE-dependent mechanisms [1]. Disturbances either in the release of mast cell mediators or in mast cell proliferation are associated with clonal mast cell disorders including monoclonal mast cell activation syndrome (MMAS) and mastocytosis respectively, which are in turn associated with some cases of anaphylaxis [2], Molecular mechanisms have been identified which may link increased releasability of mast cell mediators and conditions leading to increased mast cell numbers [3]. Patients with mastocytosis have an increased risk to develop anaphylaxis [4, 5] and those with anaphylaxis may suffer from unrecognized mastocytosis or may display incomplete features of the disease [6-8]. 

Inflammation is present in the lungs of all smokers. It is unclear why only 15% to 20% of smokers develop COPD, but susceptible individuals appear to have an exaggerated inflammatory response.5 O The inflammation of COPD differs from that seen in asthma, so the use of anti-inflammatory medications and the response to those medications are different. The inflammation of asthma is mainly mediated through eosinophils and mast cells. In COPD the primary inflammatory cells include neutrophils, macrophages, and CD8+ T lymphocytes. 

Eosinophils also tend to accumulate at the sites of allergic reactions, particularly in the lungs and skin. The functions of the eosinophils in these areas include neutralization of inflammatory mediators released from mast cells... 

Several of the postulated roles for nematode-secreted AChEs assume that they gain access to the intestinal mucosa. Several possibilities exist for transport of parasite AChE across the epithelial cell barrier, such as (i) utilization of existing pathways for receptor-mediated transcytosis (ii) a paracellular route facilitated by parasite-secreted proteases as observed for a bacterial elastase (Azghani et al., 1993) and (iii) increased paracellular permeability resulting from inflammatory events in the mucosa. We consider the latter suggestion most likely, as this has been duplicated by ex vivo perfusion with rat mast cell protease II (Scudamore et al., 1995). Moreover, cholinergic stimulation attenuates epithelial barrier properties to macromolecules in rat ileal crypts (Phillips et al., 1987). 

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