Effects of nedocromil sodium (Tilade) on the activation of human eosinophils and neutrophils and the release of histamine from mast cells.
The ability of nedocromil sodium, a new anti-inflammatory agent for the treatment of asthma, to inhibit activation of human eosinophils and neutrophils in vitro, has been studied using an adherence reaction (the "rosette" technique) as well as a cytotoxicity assay. We have also investigated the capacity of nedocromil sodium to inhibit IgE-dependent histamine release from human lung mast cells. The drug was a potent inhibitor (IC50 approx 5 x 10(-9)M) of fMLP-induced enhancement of eosinophil and neutrophil complement (C3b) and IgG (Fc) rosettes. There was also a comparable inhibition of enhancement, by fMLP, of eosinophil and neutrophil cytotoxicity (for complement-coated schistosomula of Schistosoma mansoni). Although nedocromil sodium also inhibited histamine release from human lung mast cells in a dose-dependent fashion its activity was relatively weak (IC30 5 x 10(-6)M) compared to its effect on granulocytes. These experiments support the view that the principal mode of action of nedocromil sodium is its capacity to inhibit the activation of inflammatory cells.
Moqbel
R
R
Department of Allergy & Clinical Immunology Cardiothoracic Institute, Brompton Hospital London, England.
Cromwell
O
O
Walsh
G M
GM
Wardlaw
A J
AJ
Kurlak
L
L
Kay
A B
AB
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D003179:Complement C3b / Q000032:analysis; D004305:Dose-Response Relationship, Drug; D004804:Eosinophils / Q000502:physiology*; D006636:Histamine Release / Q000187:drug effects*; D006801:Humans; D008407:Mast Cells / Q000378:metabolism*; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D017835:Nedocromil; D009504:Neutrophils / Q000502:physiology*; D011804:Quinolines / Q000494:pharmacology*; D012397:Rosette Formation; D013997:Time Factors
D000894:Anti-Inflammatory Agents, Non-Steroidal; D011804:Quinolines; D017835:Nedocromil; D009240:N-Formylmethionine Leucyl-Phenylalanine; D003179:Complement C3b