To investigate the role of IL-5 in airway hyperreactivity and pulmonary 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 10/0 ovalbumin (OVA) aerosol and assessed for airway eosinophilia (by bronchoalveolar lavage [BAL] and histologic evaluation of airway tissue) and bronchoconstrictor responsiveness to substance P (SP)(as RL100 and Cdyn40) 24 h later. OVAchallenge of sensitized animals caused a significant increase in airway responsiveness to S~ with a 4.9-fold decrease in RL100 and a 4.7-fold decrease in Cdyn40• Accompanying this increased sensitivity to SP was a 9-fold increase in eosinophils recovered in BAL and a 4-to 5-fold increase in eosinophils in intrapulmonary bronchial tissue. Intraperitoneal treatment with 10 mg/kg of the IL-5 antibody 2 h before OVAchallenge blocked BAL and lung tissue increases in eosinophils but had no effect on the development of airway sensitivity to SR 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 accumulation of eosinophils within the lung of the guinea pig. Mauser PJ, Pitman A, Witt A, Fernandez X, Zurcher J, Kung T, Jones H, Watnick AS, Egan RW, Kreutner W, Adams GK III. Inhibitory effect of the TRFK-5 anti-IL-5 antibody in a guinea pig model of asthma. Am Rev Respir Dis. 1993; 148: 1623-7.

Data from several clinical studies correlate eosinophilia with asthma. Analyses of lung tissues derived from patients who died in status asthmaticus demonstrated tissue eosinophilia and other morphologic features of inflammation, including basement membrane thickening and mucus plugging (1-3). Furthermore, the presence of elevated eosinophils in bronchoalveolar lavage (BAL) fluid and/or peripheral blood correlates with the severity of the disease (4-8). Allergic asthmatic patients who develop a late-phase obstruction after antigen challenge demonstrate both increased airway eosinophils and an increase in airway hyperreactivity (9-12). It therefore seems that an increase in lung and blood eosinophil levels may be associated with asthma. Because they produce eosinophilic infiltration of the airways, granulocyte-macrophage colony-stimulating factor, interleukin-3 (IL-3), and interleukin-5 (IL-5) are thought to contribute to the airway inflammation found in asthma (13-15). Of these cytokines, IL-5 is the most closely correlated with eosinophilia because it is associated with eosinophilopoiesis, eosinophil chemoattraction, prolongation of eosinophil survival, and eosinophil activation (15-17). Furthermore, an antibody to IL-5 blocks allergic pulmonary eosinophilia in guinea pigs (17). However, this earlier study did not investigate changes in airway responsiveness after antigen challenge.