Impaired cytokine production of circulating immune cells in severe asthma in response to Influenza virus

Abstract

<b>Background:</b> Severe asthma patients are more susceptible to infections with the influenza virus (IAV) than healthy subjects. This suggests defects in the immune response to IAV and would be critical for IAV-induced exacerbations. Circulating immune cells get recruited to the draining lymph nodes and/or the infected tissue and then get activated in acute IAV infections. <b>Hypothesis:</b> IAV-induced activation of circulating leukocytes is impaired in severe asthma. <b>Methods:</b> Peripheral blood mononuclear cells from 19 healthy non-smokers (NS) and 55 non-smokers with severe asthma (SA) were ex vivo infected with IAV H1N1 at MOIs 0.1 and 1.0. After 24h and 7d, cytokines (activity markers) were measured in cell culture supernatants by ELISA. Data were normalized to baseline and compared between NS and SA. <b>Results:</b> Baseline IFNα, IL6, TNFα, IL1β, IL8, and IFNγ were decreased, CCL2 was increased, and CCL5 showed no differences in SA vs. NS. IAV induced IFNα, IL6, CCL2, and CCL5 after 24h and 7d, TNFα, and IL8 after 24h, and IL1β after 7d in NS. IAV-induced IL8, CCL2, IFNγ, and TNFα (7d) were increased, but IAV-induced IFNα, TNFα (24h), and CCL5 were reduced in SA vs. NS. For IL6 and IL1β there were no differences between the groups. <b>Conclusion:</b> Impaired cytokine responses to acute IAV infection could explain the increased susceptibility to IAV in asthma and the increase in inflammation in exacerbations. This implicates a systemic immunodeficiency leading to an impaired activation of circulating leukocytes after recruitment to the infected tissue.