HRV Reduces Cytokine Production in Severe Asthma Patients

Kaschin Jamal Jameel

Patients with severe asthma have an increased susceptibility to respiratory tract infections with rhinovirus (HRV) causing asthma exacerbations, implying defects in immune responses.

In new data presented virtually at the European Respiratory Society (ERS) 2020 International Congress, a team, led by Kaschin Jamal Jameel, examined with HRV-induced activation of circulating leukocytes is suppressed in severe asthma and influenced by type-2 inflammation.

The researchers examined peripheral blood mononuclear cells (PBMCs) from 19 healthy participants who never smoked and 34 individuals who do not smoke but are suffering from severe asthma. Each individual was ex vivo infected with HRV 16 at MOIs 0.1 and 1.0.

They measured cytokines (activity markers) in cell culture supernatants by ELISA after 24 hours and 7 days. The researchers normalized data to baseline and compared between the healthy control group and the asthma group. They then analyzed the data for correlation with total IgE (n = 31 severe asthma) and with type-2 inflammation markers blood eosinophils (n = 32 severe asthma), FeNO (n = 25 severe asthma) and serum-periostin (n = 29 severe asthma).

The investigators found that baseline IL6, IL8, TNFα and IFNγ were reduced, while IL1β was increased in the asthma group when compared to the healthy group.

They also identified HRV induced IFNα, IL1β, IL6, TNFα, CCL2, and CCL5 after 24 hours and 7 days and IL8 and IFNγ after 7 days in the never smoked group.

Other than IFNy, HRV-induced cytokine responses were reduced in the severe asthma group compared to the healthy never smoking group, while the IL6 response was lower in the asthma arm with <300 than in the same group with ≥300 eosinophils/μl blood.

HRV-induced IFNα, IL1β and CCL2 correlated negatively to FeNO, periostin or both, respectively.

“Cytokine production of leukocytes in response to HRV is reduced in severe asthma,” the authors wrote. “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.”

While it is clear that air pollution has a negative impact on the overall health of individuals, it is not entirely clear how air pollution is associated with urgent hospitalizations in a separate ERS 2020 study.

The risk of urgent respiratory hospitalizations (76 events) was significantly linked to increasing NO2 at lag 4 (OR, 1.26; 95% CI, 1.02-1.56), lag 5 (OR, 1.45; 95% CI, 1.05-2.01), and lag 6 (OR, 1.67; 95% CI, 1.05-2.65).

The risk of cardiovascular hospitalizations were also associated with increasing PM10 at lag 0 (OR, 1.77; 95% CI, 1.11-2.82) and up to lag 3 in Pisa (55 events), and with increasing NO2 at lag 0 (OR, 1.80; 95% CI,1.07-3.01) and lag 1 (OR, 1.50; 95% CI, 1.04-2.17) in Cascina (82 events).

The study, “Rhinovirus-induced cytokine production of circulating leukocytes is reduced in severe asthma,” was published online by ERS 2020.