Interleukin-15 Overexpression Protect Mice from the Allergen-Induced Airway Obstruction
Saturday, March 5, 2016
South Exhibit Hall H (Convention Center)
Sathisha Upparahalli Venkateshaiah, PhD, Murli Manohar, Chandrashekara Puthanapura Mahadevappa, PhD, Anil Mishra, PhD FAAAAI
Rationale: Diagnosis of chronic obstructive pulmonary disorder is associated with asthma in older patients suggesting that long-standing asthma may lead to irreversible airflow obstruction. Recently, we developed our interest in interleukin IL-15 in age associated asthma pathogenesis. Since, IL-15 protein levels decline progressively with advanced age in mice and IL-15 association and its deficiency is reported in human asthma. Therefore, a great need to continue with innovative fundamental studies to uncover new possibilities for the therapeutic interventions for airway hyperactivity/obstruction.

Methods: Airway hyperreactivity in allergen challenged rIL-15 treated, non-treated mice and IL-15 overexpressed mice were measured by whole body plethysmography and resistance (RI)/compliance (cdyn) by using Aeroneb® Lab nebulizer system. The cytokines levels were measured by performing ELISA analysis.

Results: rIL-15 delivery to the lung in murine model of asthma protects airway hyperreactivity (PENH response), improves airway resistance (RI), compliance (cdyn) and also downregulates the levels of pro-inflammatory cytokines like IL-4, IL-5, IL-13.  In addition, we observed that DOX-inducible CC-10-IL-15 bi-transgenic mice were protected from the induction of Aspergillus extract-induced experimental asthma. The 3 weeks DOX exposed allergen challenged IL-15 bi-transgenic mice show significant reduced airway hyperactivity (PENH response) and resistance (RI), pro-inflammatory cytokines like IL-5, IL-13, goblet cell hyperplasia and also collagen accumulation in the lung compared to no DOX treated allergen challenged IL-15 bi-transgenic mice. 

Conclusions: Taken together, we first time report that IL-15 immunotherapy may be a novel therapeutic strategy to improve airway obstruction and resistance in food or environmental allergens induced chronic asthma.