Nedocromil sodium prevents in vivo generation of the eosinophilotactic substance induced by PAF but fails to antagonize its effects.
1 The intrathoracic injection of platelet activating factor (PAF) into rats induced a decrease in the pleural leucocyte numbers within 15 min, accompanied by a marked exudation, maximal 1 h later. After 6 h, concomitantly with the reduction of exudation, a marked increase in the number of mononuclear cells, neutrophils and eosinophils was observed. Within 24 h, the pleural eosinophil accumulation peaked and persisted up to 96 h. 2 Topical treatment with nedocromil sodium affected pleural exudation by PAF under conditions where systemic meclizine was ineffective. Nedocromil sodium blocked, dose-dependently, the increase in the pleural content of mononuclear cells, neutrophils and eosinophils, observed 6 h after PAF administration, as well as the eosinophilia 24 h later. Moreover, the co-incubation of peritoneal eosinophils with nedocromil sodium did not interfere with the migration triggered by PAF. 3 The transfer of the 6 h-PAF pleural washings from donor to recipient rats caused a selective pleural eosinophilia, which was clearly inhibited when nedocromil sodium was administered to donor, but not to recipient animals, showing that this drug interferes with the generation rather than with the expression of the eosinophilotactic activity(ies). 4 These findings indicate that the nedocromil sodium interferes with PAF-induced exudation and leucocyte accumulation, by a mechanism other than its ability to reduce the local effects of histamine and which may relate to suppression of the eosinophilotactic principle generation.
e Silva
P M
PM
Departamento de Fisiologia e Farmacodinâmica, Instituto Oswaldo Cruz/FIOCRUZ, Rio de Janeiro, Brazil.
Martins
M A
MA
Castro-Faria-Neto
H C
HC
Bozza
P T
PT
Pires
A L
AL
Cordeiro
R S
RS
Vargaftig
B B
BB
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D004804:Eosinophils / Q000187:drug effects; D005260:Female; D006632:Histamine / Q000494:pharmacology; D007958:Leukocyte Count; D008222:Lymphokines / Q000096:biosynthesis*; D008297:Male; D017835:Nedocromil; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D010998:Pleurisy / Q000139:chemically induced / Q000378:metabolism; D011506:Proteins / Q000378:metabolism; D015363:Quinolones / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains
D000894:Anti-Inflammatory Agents, Non-Steroidal; D008222:Lymphokines; D010972:Platelet Activating Factor; D011506:Proteins; D015363:Quinolones; C022227:eosinophil stimulating promoter; D017835:Nedocromil; D006632:Histamine