Inhibition by nedocromil sodium of recombinant human interleukin-5-induced lung hyperresponsiveness to platelet-activating factor in actively sensitized guinea pigs.
BACKGROUND
The intratracheal instillation of recombinant human interleukin-5 (rhIL-5) into isolated lungs from sensitized and antigen-boosted guinea pigs is followed by enhanced responses to platelet-activating factor (PAF).


METHODS
Modulation by nedocromil sodium of rhIL-5-dependent hyperresponsiveness to PAF was investigated. Perfused lungs from guinea pigs actively sensitized to ovalbumin were injected intratracheally with 300 ng rhIL-5 followed by PAF (10 and 100 ng intraarterially).


RESULTS
No inhibition of rhIL-5-induced increased bronchoconstriction and release of thromboxane (TX)B2 and histamine by PAF was observed when nedocromil sodium (10 mumol/L) was perfused into the lungs. In contrast, when guinea pigs were treated for 2 days (30 mg/kg twice a day), eosinophil recruitment into the bronchoalveolar lavage fluid and hyperresponsiveness to PAF were markedly reduced (100% [p < 0.001]; around 70% [p < 0.05] and around 90% [p < 0.001] inhibition for bronchoconstriction, TXB2 and histamine release, respectively).


CONCLUSIONS
Our results indicate that nedocromil sodium prevents the rhIL-5-induced lung hyperresponsiveness to PAF and the eosinophil migration into the airways only when it is administered in vivo. It is thus suggested that nedocromil sodium interferes with the development of airway inflammation by inhibiting the recruitment in the lung of a target on which PAF and IL-5 interact.
Pretolani
M
M
Unité de Pharmacologie Cellulaire Unité Associée Institut Pasteur/INSERM no. 285, Paris, France.
Lefort
J
J
Vargaftig
B B
BB
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D016535:Bronchial Hyperreactivity / Q000276:immunology / Q000517:prevention & control*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D016084:Bronchoconstriction; D002634:Chemotaxis, Leukocyte / Q000276:immunology; D004804:Eosinophils / Q000276:immunology; D006168:Guinea Pigs; D006636:Histamine Release; D015848:Interleukin-5 / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D008297:Male; D017835:Nedocromil; D010972:Platelet Activating Factor / Q000494:pharmacology*; D015363:Quinolones / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors / Q000494:pharmacology; D013929:Thromboxane B2 / Q000032:analysis
D000894:Anti-Inflammatory Agents, Non-Steroidal; D015848:Interleukin-5; D010972:Platelet Activating Factor; D015363:Quinolones; D011994:Recombinant Proteins; D017835:Nedocromil; D013929:Thromboxane B2