Methods: To investigate the individual effects of specific anti-type2-antibodies on murine asthma features induced by intranasal type2 cytokine application Bl/6 mice received IL-5 and IL-13 (76.3 pmol each) intranasally. Blocking antibodies specific for IL-5 or IL-13 (100 µg/animal/timepoint) were administered twice. Cellular and functional asthma features were analyzed 72 hours after cytokine application.
Results: IL-13 or IL-5+IL-13 treated animals developed an airway hyperreactivity (airway resistance at methacholine 100 mg/ml: 90.6±55.7 in PBS mice, 201.5±71.5% in IL-13 treated mice (n=4)) and goblet cell metaplasia. IL-5 alone and in combination with IL-13 increased bone marrow eosinophils (6.16±1.27% eosinophils in PBS mice (n=20), 10.5±1.9% in IL-5 mice (n=11), 12.4±1.4% in IL-5+IL-13 mice (n=11)). Similarly, synergistic application of IL-5+IL-13 enhanced BAL eosinophil numbers (0.16±027% in PBS mice, 9.27±5.65% in IL-5+IL-13 mice). AHR and goblet cell metaplasia were suppressed by additional injection of anti-IL-13 blocking antibodies (airway resistance: 90.38 ±35.36%) whereas anti-IL-5 antibodies strongly inhibited eosinophil influx into the bronchoalveolar space (4.26±3.1%).
Conclusions: Blocking key type2 cytokines is an effective strategy to treat cytokine-induced asthma. Antibodies against type2 cytokines IL-5 and IL-13 differ in their individual effect on murine asthma features.