Nedocromil sodium inhibits T-cell function in vitro and in vivo.
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.
Allergy-Immunology Unit, Meir General Hospital, Kfar Saba, Israel.
Y A
YA
Mekori
D
D
Baram
A
A
Goldberg
R
R
Hershkoviz
T
T
Reshef
D
D
Sredni
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D002448:Cell Adhesion / Q000276:immunology; D003877:Dermatitis, Contact / Q000276:immunology; D004139:Dinitrofluorobenzene; D016326:Extracellular Matrix Proteins / Q000276:immunology; D005260:Female; D007376:Interleukin-2 / Q000276:immunology; D008198:Lymph Nodes / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D008934:Mitogens; D017835:Nedocromil; D015363:Quinolones / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016326:Extracellular Matrix Proteins; D007376:Interleukin-2; D008934:Mitogens; D015363:Quinolones; D014409:Tumor Necrosis Factor-alpha; D017835:Nedocromil; D004139:Dinitrofluorobenzene; D002118:Calcium