Local reactivation of memory T cells results in infiltration of eosinophils and neutrophils into the airways – a mouse model for severe asthma?

Einleitung: Asthma is one of the most common chronic inflammatory diseases affecting more than 300 Million people worldwide. Globally, the economic burden associated with asthma exceeds those of HIV/AIDS and tuberculosis together annually producing direct medical and indirect costs of ca. €18 Billion for Europe alone. Remarkably, the economic burden of asthma disproportionally affects those with the most severe form of the disease. Even though patients with severe asthma represent just 10% of all asthmatics, they account for more than 50% of all direct and indirect costs. The high amount of costs is based on the severity of the disease, which frequently necessitates hospitalization and intensive medical care. This situation is even worsened by the unavailability of effective medication, a problem that arises from the fragmentary understanding of the immunopathogenesis of severe asthma and the lack of suitable animal models reflecting the complex inflammatory phenotype of this disease. Methoden: BALB/c mice were immunized against ovalbumin (OVA) by three injections of an aqueous OVA-PBS solution emulsified in complete Freund's adjuvans (CFA) on days 1, 14, and 21. Subsequently, an aqueous OVA-PBS solution containing interleukin-18 (IL-18) was applied intra-nasally (i.n.) on days 26 and 27 in order to induce local inflammation of the airways. Assessment of lung function involved methacholine provocation testing in a head-out body plethysmograph. The inflammatory response in the lung was characterized by analysing broncho-alveolar lavage (BAL) samples and inflation-fixed specimens of lung tissues. Ergebnisse: Short-term exposure of OVA-immunized BALB/c mice to OVA combined with IL-18 by two intra-nasal applications resulted in marked infiltration of both neutrophils and eosinophils into the broncho-alveolar lumen as well as into the airway wall. Furthermore, this was accompanied by pronounced reactivity to methacholine indicating the development of airway hyperresponsiveness (AHR). Diskussion: Recent studies strongly suggest that severe asthma has a distinct pathobiology that is not merely an aggravation of the processes responsible for mild-to-moderate asthma. Since in severe asthmatics neutrophils correlate with disease severity these cells are believed to play a critical role the formation of severe asthma. By displaying a mixed inflammatory response in the airways consisting of neutrophils and eosinophils together with the development of AHR this mouse model reflects two major hallmarks of human severe asthma. Thus, it could represent a useful tool for the investigation of the immunopathogenesis of this disease.

Supported by the Cluster of Excellence “Inflammation at Interfaces“ (EXC306-DW2)