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)

Nedocromil sodium, a topical antiinflammatory agent recommended as a prophylactic regimen for asthma, is known to inhibit both allergic and nonallergic inflammatory processes in which an essential role for T cells has been implicated. Therefore the direct effects of this drug on several aspects of T-cell activity were analyzed in the present study. By using murine lymphocytes we found that NS at concentrations of 10(-8) to 10(-6) mol/L inhibited the mitogen- or antigen-induced proliferative responses of these cells. It is interesting to note that higher concentrations were ineffective. Preincubation of immune lymph node cells from contact sensitized mice with the drug abrogated their ability to transfer contact sensitivity to naive recipients, an effect that was found to be specific for the treated cells. Nedocromil sodium also interfered with the mitogen-induced interleukin-2 and tumor necrosis factor production by T cells and with their ability to adhere to the bound protein components of the extracellular matrix laminin and fibronectin. All these effects may be attributed to the inhibition of the increase of cytosolic calcium, which accompanies the early phase of T-cell activation and which is an essential step in inducing the aforementioned phenomena.
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PMID:Nedocromil sodium inhibits T-cell function in vitro and in vivo. 838 27

We have previously demonstrated that histamine release from immunologically activated mast cells (MC) is enhanced by their preincubation (1 h) with interleukin-2(IL-2), and that IL-2 induces slow-chronic histamine release by MC in long-term cultures (6 days). In the present study we assessed whether nedocromil sodium can interfere with IL-2 modulation of MC histamine release. IL-2 enhancing effects nedocromil sodium activity were studied in cocultures of rat peritoneal MC with 3T3 fibroblasts (MC/3T3). MC/3T3 were preincubated for 1 h with IL-2 (50 micrograms/ml) and activated with either rabbit anti-rat IgE or compound 48/80. In chronic experiments MC/3T3 were long-term (5-6 days) incubated with IL-2 (50 micrograms/ml). Nedocromil sodium was used at 10(-5) M. MC activation both when added during the preincubation period (no tachyphylaxis was present) and when added together with the MC activators (30-50% inhibition). Washing out IL-2 before addition of the anti-IgE antibodies did not affect its histamine-release enhancing activity. Removal of nedocromil sodium before addition of the stimulus completely abrogated its effect. Continuous presence of IL-2 in the culture medium enhanced spontaneous histamine release by 37% and this effect was completely abolished in the presence of nedocromil sodium. Furthermore, nedocromil sodium decreased MC basal histamine release by 23% in long-term cocultures. Since IL-2 is known to be elevated in some pathological conditions, our results show that nedocromil sodium inhibits MC activation in an in vitro system which may represent a close resemblance to the in vivo allergic response.
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PMID:Modulations of histamine release from mast cells by interleukin-2 is affected by nedocromil sodium. 858 84