Dual mechanism of action of T2 inhibitor therapies in virally induced exacerbations of asthma: evidence for a beneficial counter-regulation.

Efthimiou, John; Poll, Chris; Barnes, Peter J

Biological agents such as omalizumab and monoclonal antibodies that inhibit type 2 immunity significantly reduce exacerbations, which are mainly due to viral infections, when added to inhaled corticosteroids in patients with severe asthma. The mechanisms for the therapeutic benefit of type 2 inhibitors in reducing virally-induced exacerbations, however, remain to be fully elucidated. Preclinical and clinical evidence supports the existence of a close counter-regulation of the high-affinity IgE receptor and interferon pathways, and a potential dual mechanism of action and therapeutic benefit for omalizumab and other type 2 inhibitors that inhibit IgE activity, which may enhance the prevention and treatment of virally-induced asthma exacerbations. Similar evidence regarding some novel type 2 inhibitor therapies, including biological and small molecule inhibitors, suggest that such a dual mechanism of action with enhancement of interferon production working through non-IgE pathways, might also exist. The specific mechanisms for this dual effect could be related to the close counter-regulation between type 2 and type 1 immune pathways and potential key underlying mechanisms are discussed. Further basic research and better understanding of these underlying counter-regulatory mechanisms could provide novel therapeutic targets for the prevention and treatment of virally-induced asthma exacerbations, as well as type 2 and non-type 2 driven asthma. Future clinical research should examine the effects of type 2 inhibitors on interferon responses and other type 1 immune pathways, in addition to any effects on the frequency and severity of viral and other infections and related exacerbations in patients with asthma as a priority.