BACKGROUND:Asthma prevalence has increased world-wide especially in children; thus there is a need to develop new therapies that are safe and effective especially for patients with severe/refractory asthma. CD4(+) T cells are thought to play a central role in disease pathogenesis and associated symptoms. Recently, TRPV1 has been demonstrated to regulate the activation and inflammatory properties of CD4(+) cells. The aim of these experiments was to demonstrate the importance of CD4(+) T cells and the role of TRPV1 in an asthma model using a clinically ready TRPV1 inhibitor (XEN-D0501) and genetically modified (GM) animals.
METHODS:Mice (wild type, CD4 (-/-) or TRPV1 (-/-)) and rats were sensitised with antigen (HDM or OVA) and subsequently topically challenged with the same antigen. Key features associated with an allergic asthma type phenotype were measured: lung function (airway hyperreactivity [AHR] and late asthmatic response [LAR]), allergic status (IgE levels) and airway inflammation.
RESULTS:CD4(+) T cells play a central role in both disease model systems with all the asthma-like features attenuated. Targeting TRPV1 using either GM mice or a pharmacological inhibitor tended to decrease IgE levels, airway inflammation and lung function changes.
CONCLUSION:Our data suggests the involvement of TRPV1 in allergic asthma and thus we feel this target merits further investigation.
