235
Individual and Synergistic Effects of IL-5 and IL-13 on Trans-Compartmental Activation and Migration of Eosinophils and Murine Asthma Features
Saturday, March 5, 2016
South Exhibit Hall H (Convention Center)
Sebastian Reuter, Helen Meyer-Martin, Hendrik Beckert, Stephanie Korn, Roland Buhl
Rationale:

The type 2 cytokines IL-5 and IL-13 are central to asthma pathogenesis, and innovative therapeutic approaches focus on strategic inhibition of these mediators.

Methods:

To analyze the individual and synergistic effects of these cytokines Bl/6 mice were treated intranasally with IL-5 (76.3 pmol, n=11) and IL-13 (76.3 pmol, n=11) alone and in combination (n=11). After 72 h pulmonary function as well as cytokine-induced inflammatory changes in bone marrow (BM), blood, lung tissue and bronchoalveolar lavage (BAL) were investigated.

Results:

Single application of IL-5 particularly led to a distinct increase of eosinophils and their precursors in the BM (6.16±1.27% eosinophils in PBS mice versus 10.52±1.93% in IL-5 mice), whereas application of IL-13 promoted airway hyperreactivity (airway resistance at methacholine 100 mg/ml: 90.56±55.65% change from baseline in PBS mice versus 201.5±71.48% in IL-13 treated mice) with a slight increase of lung eosinophils and the development of goblet cell metaplasia. In contrast to single cytokine application combinations of IL-5 + IL-13 further enhanced eosinophil numbers in all compartments (BM: 12.4±1.43%, blood: 7.22±1.74%, lung: 6.93±1.65%, BAL: 8.89±6.20%).

Conclusions:

These results illustrate for the first time the effects of single and synergistic intranasal application of type 2 cytokines IL-5 and IL-13 on cellular and functional murine asthma features in a comparative manner and illustrate the individual contribution of each cytokine on type 2 cytokine induced murine asthma.