Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: KEGG:D00527 (Nedocromil sodium)
 190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Using the allergen-induced late-phase asthmatic reaction as a working model, we studied the activity of certain inflammatory cells and their reaction to nedocromil sodium. The processes that were examined in vitro included the following: the chemotaxis of purified neutrophils and eosinophils, the early steps of neutrophil and eosinophil activation, and the release of mediators from these cells. Nedocromil sodium strongly inhibited neutrophil mobilization caused by four chemotactic factors (zymosan activated serum, N-formyl-methionyl-leucyl-phenylalanine platelet-activating factor [PAF], and leukotriene B4 [LTB4] and eosinophil mobilization caused by two factors (PAF and LTB4). In vitro treatment of eosinophils from normal subjects with picomolar concentrations of interleukin-3, interleukin-5, or granulocyte-macrophage colony stimulating factor increased the chemotactic responsiveness toward PAF and LTB4 and induced a chemotactic responsiveness toward N-formyl-methionyl-leucyl-phenylalanine and neutrophil activating factor/interleukin-8. The zymosan activated serum-induced chemotactic responsiveness remained unaltered. Nedocromil sodium inhibited the cytokine-primed chemotactic responsiveness to the various chemotaxins, not the influence of the cytokines on the cells. Activation of granulocytes, as measured by Ca2+ influx, was not inhibited by nedocromil sodium. Mediator formation in eosinophils was modified only slightly. These results suggest that inhibiting the mobilization of inflammatory cells in the lung tissue may be an important action of nedocromil sodium. Therefore these effects may be relevant to the treatment of asthma given the role of airway inflammation in this disease process.
 ...
PMID:Effects of nedocromil sodium on in vitro induced migration, activation, and mediator release from human granulocytes. 839 21

The pharmacological activity of nedocromil sodium is extensive and the compound should affect a variety of inflammatory processes by preventing activation of the involved cells or blocking release of their mediators. Some in vitro actions of nedocromil sodium are particularly relevant to the mechanisms of allergic rhinitis, and the response of the nasal epithelium to pollutants such as ozone. The effects of nedocromil sodium on mucosal mast cells, eosinophils, sensory nerves and nasal epithelial cells can each be linked to its potential clinical effectiveness by our own biopsy studies from patients with active allergic rhinitis. Nedocromil sodium has been shown to modulate production of a number of powerful cytokines, such as GM-CSF and TNF alpha, which are produced by the human nasal epithelium, as well as by involved inflammatory cells and lymphocytes, and which orchestrate the inflammatory response to allergen or to pollutant provocation. So, in addition to inhibiting activated mast cells and eosinophils, nedocromil sodium acts on the nasal epithelium itself to prevent further accumulation of these cells and thus to break the inflammatory chain of events. On this evidence of its preclinical activity, nedocromil sodium promises to become a very useful topical treatment for allergic rhinitis.
 ...
PMID:Clinical implications of the pharmacological profile of Tilarin. 865 76

The bronchial epithelium produces cytokines that could contribute to inflammatory events in airways. In this study we determined the basal and TNFalpha stimulated productions of GM-CSF and IL-8 by human bronchial epithelial cells (HBEC) collected from 12 control and six asthmatic patients. Spontaneous and TNFalpha-induced GM-CSF or IL-8 released levels increased significantly with time. Epithelial cells from asthmatic patients spontaneously released high levels of GM-CSF (24 h). TNFalpha potentiated GM-CSF and IL-8 release in control subjects and only the IL-8 production in asthmatics. Nedocromil sodium, an antiinflammatory drug, and salbutamol, a beta2-agonist, are commonly used in asthma. They were evaluated on the spontaneous and TNF-induced expression of GM-CSF and IL-8 in cultured bronchial epithelial cells. Nedocromil sodium, at the concentration of 10(-6) M, reduced the TNF-induced increase in GM-CSF but not the IL-8 release. Salbutamol, at the concentration of 10(-6) or 10(-5) M, did not affect the constitutive or stimulated production of both cytokines.
 ...
PMID:Granulocyte-macrophage colony stimulating factors (GM-CSF) and interleukin 8 (IL-8) production by human bronchial epithelial cells (HBEC) in asthmatics and controls. Lack of in vitro effect of salbutamol compared to sodium nedocromil. 882 Feb 49

The effect of interleukin (IL)-2 on eosinophil survival and mediator release was investigated in vitro. Human peripheral blood eosinophils were isolated and purified from mildly atopic donors and cultured on albumin-coated wells with different concentrations of IL-2, interferon (IFN)-gamma, and granulocyte-macrophage colony stimulating factor (GM-CSF) and their viability was evaluated after 4 days in culture. Eosinophils were cultured with IL-2 (1000 u/ml), IFN-gamma (1000 u/ml), or GM-CSF (10 ng/ml) for 18 h, or with platelet activating factor (PAF) (10(-6) M) for 20 min, and the release of eosinophil peroxidase (EPO) and IL-6 was measured. Nedocromil sodium (10(-5) M) was added with each of the above cytokines to study the inhibitory effect of this drug on EPO release. A significant increase of EPO release was induced by IL-2, IFN-gamma, and GM-CSF after 18 h in culture. IL-2 as well as IFN-gamma induced a significant IL-6 release from eosinophils. Nedocromil sodium significantly inhibited EPO release from eosinophils induced by IL-2 or PAF. These results show that IL-2 can activate peripheral blood eosinophils to release granule mediators (EPO) and cytokines (IL-6). Taken together with the presence of IL-2 receptors on eosinophils, we conclude that IL-2 is an important mediator in allergic inflammation and a possible target for pharmacological modulation.
 ...
PMID:Interleukin-2 activates human peripheral blood eosinophils. 1152 78