EFFECTS OF AN ANTIBODY TO INTERLEUKIN-5 IN A MONKEY MODEL OF ASTHMA

To investigate the role of interleukin-5 (IL-5) on airway hyperreactiv ity and pulmonary inflammation in nonhuman primate airways, the effect of a neutralizing monoclonal antibody to murine IL-5 (TRFK-5) was inv estigated in a cynomolgus monkey model of allergic asthma. Anesthetize d Ascaris-sensitive monkeys underwent bronchoalveolar lavage (BAL) to assess the granulocyte content of this fluid before and 24 h after aer osolized Ascaris suum extract inhalation. Airway reactivity was assess ed by the concentration of inhaled histamine required to produce a 40% reduction in dynamic lung compliance (Cdyn(40)). Exposure to A. suum extract produced an increase in airway reactivity (Cdyn(40) = 0.065 +/ - 0.024% before Ascaris; Cdyn(40) = 0.014 +/- 0.004% after Ascaris) an d an inflammatory reaction in the airways characterized by an increase in BAL eosinophils (0.05 +/- 0.03 x 10(3) cells/ml before Ascaris; 17 6 +/- 76 x 10(3) cells/ml after Ascaris) and neutrophils (3 +/- 1 x 10 (3) cells/ml before Ascaris; 406 +/- 211 x 10(3) cells/ml after Ascari s). In contrast, only small nonsignificant changes in airway reactivit y and granulocyte influx into the BAL occurred after aerosolized salin e as a sham challenge. When the monkeys were treated 1 h before Ascari s challenge with the TRFK-5 antibody (0.3 mg/kg, intravenously), there was no increase in airway reactivity after Ascaris challenge (Cdyn(40 ) = 0.032 +/- 0.016% before Ascaris; Cdyn(40) = 0.217 +/- 0.196% after Ascaris) and there were only small increases in the number of eosinop hils and neutrophils in the BAL after Ascaris challenge. The inhibitio n of this pulmonary eosinophilia and bronchial hyperresponsiveness by TRFK-5 was seen for up to 3 mo after treatment. These results demonstr ate the importance of IL-5 and the inhibitory effects of an anti-IL-5 antibody on the induction of allergic pulmonary inflammation and airwa y hyperreactivity in nonhuman primates.