INHIBITORY EFFECT OF THE TRFK-5 ANTI-IL-5 ANTIBODY IN A GUINEA-PIG MODEL OF ASTHMA

To investigate the role of IL-5 in airway hyperreactivity and pulmonar y eosinophilia, we used a model of allergic asthma in guinea pigs and a neutralizing monoclonal antibody (TRFK-5) directed against murine IL -5. Sensitized guinea pigs were challenged with 1% ovalbumin (OVA) aer osol and assessed for airway eosinophilia (by bronchoalveolar lavage  BAL and histologic evaluation of airway tissue) and bronchoconstricto r responsiveness to substance P (SP) (as RL(100) and Cdyn(40)) 24 h la ter. OVA challenge of sensitized animals caused a significant increase in airway responsiveness to SP, with a 4.9-fold decrease in RL(100) a nd a 4.7-fold decrease in Cdyn(40). Accompanying this increased sensit ivity to SP was a 9-fold increase in eosinophils recovered in BAL and a 4- to 5-fold increase in eosinophils in intrapulmonary bronchial tis sue. Intraperitoneal treatment with 10 mg/kg of the IL-5 antibody 2 h before OVA challenge blocked BAL and lung tissue increases in eosinoph ils but had no effect on the development of airway sensitivity to SP. In contrast, similar treatment with 30 mg/kg of this antibody blocked OVA-induced increased sensitivity to SP as well as BAL and lung tissue eosinophilia. These data suggest a critical and possibly independent role for IL-5 in allergic airway hyperresponsiveness and the accumulat ion of eosinophils within the lung of the guinea pig.