Protection by nedocromil sodium of active immunization-induced bronchopulmonary alterations in the guinea pig.
The effect of nedocromil sodium on PAF-acether- and antigen-induced bronchoconstriction (BC) and mediator release in lungs from actively sensitized guinea pigs and on the eosinophil content of bronchoalveolar lavage (BAL) was investigated. Guinea pigs were actively sensitized by two subcutaneous injections of 10 micrograms ovalbumin in 1 mg AI(OH)3 at 2-wk intervals. One week after the second (booster) injection, the lungs were removed, perfused in the absence or presence of indomethacin, and challenged at 10-min intervals with PAF-acether (1 and 100 ng) and with ovalbumin (1 micrograms). No inhibition of PAF-acether- and antigen-induced BC or mediator release from sensitized lungs was observed when nedocromil sodium (10 microM) was added directly to the buffer solution. By contrast, when guinea pigs were treated for 1 wk before the experiment with nedocromil sodium (30 mg/kg per day), BC and the release of leukotrienelike material (but not of thromboxane B2) to 1 ng PAF-acether were reduced by around 50% (p less than 0.05) and 62% (p less than 0.05), respectively. No inhibition was observed for 100 ng PAF-acether and 1 micrograms ovalbumin. Furthermore, nedocromil sodium markedly impaired histamine secretion induced by both PAF-acether and antigen administration. Nedocromil sodium did not affect the titers of circulating ovalbumin-specific immunoglobulin G, as detected by an enzyme-linked immunosorbent assay. The 1-wk treatment with nedocromil sodium also reduced markedly the proportion of eosinophils in the BAL of sensitized guinea pigs, whereas it was ineffective when injected once subcutaneously at the dose of 30 mg/kg 2 h before the experiment.(ABSTRACT TRUNCATED AT 250 WORDS)
Pretolani
M
M
Unité de Pharmacologie Cellulaire, Unité Associée Institut Pasteur, INSERM no. 285, Paris, France.
Lefort
J
J
Silva
P
P
Malanchere
E
E
Dumarey
C
C
Bachelet
M
M
Vargaftig
B B
BB
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D001980:Bronchi / Q000187:drug effects / Q000378:metabolism; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D003251:Constriction, Pathologic; D004804:Eosinophils / Q000187:drug effects; D005260:Female; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D020024:Leukotriene Antagonists; D015289:Leukotrienes / Q000378:metabolism; D008297:Male; D017835:Nedocromil; D010047:Ovalbumin / Q000037:antagonists & inhibitors; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors / Q000276:immunology; D015363:Quinolones / Q000494:pharmacology / Q000627:therapeutic use*; D012130:Respiratory Hypersensitivity / Q000276:immunology / Q000517:prevention & control*; D013929:Thromboxane B2 / Q000378:metabolism
D000894:Anti-Inflammatory Agents, Non-Steroidal; D020024:Leukotriene Antagonists; D015289:Leukotrienes; D010972:Platelet Activating Factor; D015363:Quinolones; D017835:Nedocromil; D013929:Thromboxane B2; D010047:Ovalbumin; D007213:Indomethacin