Rhinovirus-induced cytokine production of circulating leukocytes is reduced in severe asthma

Background: Severe asthma patients have an increased susceptibility to respiratory tract infections with rhinovirus (HRV) that cause exacerbations. This implicates defects in immune responses. Method: HRV-induced activation of circulating leukocytes is suppressed in severe asthma and is influenced by type-2 inflammation. Methods: Peripheral blood mononuclear cells (PBMCs) from 19 healthy never-smokers (NS) and 34 non-smokers with severe asthma (SA) were ex vivo infected with HRV16 at MOIs 0.1 and 1.0. Cytokines (activity markers) were measured in cell culture supernatants by ELISA after 24h and 7d. Data were normalized to baseline and compared between NS and SA and were analyzed for correlation with total IgE (n=31 SA) and with the type-2 inflammation markers blood eosinophils (n=32 SA), FeNO (n=25 SA) and serum-periostin (n=29 SA). Results: Baseline IL6, IL8, TNFα and IFNγ were reduced, IL1β was increased in SA vs. NS. HRV induced IFNα, IL1β, IL6, TNFα, CCL2 and CCL5 after 24h and 7d and IL8 and IFNγ after 7d in NS. Except for IFNγ, HRV-induced cytokine responses were reduced in SA vs. NS. The IL6 response was lower in SA with Conclusion: Cytokine production of leukocytes in response to HRV is reduced in severe asthma. This implies systemic immune defects resulting in the suppression of the activation of circulating leukocytes after recruitment to the infected tissue. This might be affected by the severity of type-2 inflammation and can explain the impaired infection defense and the increased susceptibility to viral infections in asthma.