Effect of human recombinant interleukin-5 on in vitro responsiveness to PAF of lung from actively sensitized guinea-pigs.
1. The intra-tracheal (i.t.) administration of human recombinant interleukin-5 (rhIL-5; 100 or 300 ng) to isolated perfused lungs from guinea-pigs actively sensitized to ovalbumin induced an increased bronchoconstriction and release of thromboxane A2 (TXA2) and histamine into the lung effluent following the subsequent (10 min) intra-arterial injection of platelet-activating factor (PAF). Lung responses to 5-hydroxytryptamine were unaffected by rhIL-5. 2. Hyperresponsiveness to PAF was observed when the lungs were obtained from guinea-pigs used 2 or 7 days after a booster injection of the antigen and, to a lower extent, when they were from animals sensitized by a single antigen administration. By contrast, rhIL-5 did not modify the responses to PAF of lungs from passively sensitized or from adjuvant-treated guinea-pigs, suggesting that immunological stimulation is required to allow the expression of synergism between rhIL-5 and PAF. 3. Guinea-pigs killed 2 and 7 days after the booster injection of the antigen exhibited a marked increase in the number of eosinophils in the bronchoalveolar lavage fluid (BAL), as compared to non-sensitized animals. 4. Our results demonstrate that rhIL-5 and PAF act synergistically to induce enhanced bronchoconstriction and mediator release exclusively when lungs are obtained from guinea-pigs sensitized once to ovalbumin and then boosted. Since recruitment of eosinophils into the airways and the development of hyperresponsiveness to PAF are concomitant, it is suggested that eosinophils are the target cells for interaction between rhIL-5 and PAF.
Pretolani
M
M
Unité de Pharmacologie Cellulaire, Unité Associée Institut Pasteur/INSERM n. 285, Paris, France.
Lefort
J
J
Leduc
D
D
Vargaftig
B B
BB
D000818:Animals; D001980:Bronchi / Q000187:drug effects; D016535:Bronchial Hyperreactivity / Q000503:physiopathology*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D006168:Guinea Pigs; D006636:Histamine Release; D066298:In Vitro Techniques; D015848:Interleukin-5 / Q000494:pharmacology*; D008168:Lung / Q000276:immunology / Q000378:metabolism*; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D010477:Perfusion; D010972:Platelet Activating Factor / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000494:pharmacology; D012130:Respiratory Hypersensitivity / Q000503:physiopathology*; D013929:Thromboxane B2 / Q000378:metabolism
D015848:Interleukin-5; D010972:Platelet Activating Factor; D011994:Recombinant Proteins; D013929:Thromboxane B2