Characteristics of rhinovirus-induced PBMC immune responses in asthmatics, from infancy to adulthood

Background: Asthmatic patients have higher susceptibility to rhinovirus (RV) infection, the most common trigger of asthma exacerbations in children and adults. Impaired IFN-alpha and lambda production in bronchial epithelial cells from asthmatic adults upon exposure to RV has been demonstrated in vitro. However, the mechanisms underlying the increased susceptibility to RV infection in asthmatic patients are not fully understood. The aim of the present study was to investigate the characteristics of the immune responses of peripheral blood mononuclear cells (PBMCs) from asthmatic patients to RV stimulation.

Methods: PBMCs obtained from three different age groups (1-6y: young children group; 7-19y: youth group; 20-y: adult group) of asthmatic patients and non-asthmatic control subjects were stimulated with RV14 for 72 h. Healthy adults with a history of childhood asthma were also enrolled. The concentrations of IFN-alpha, IL-6, TNF-alpha, IL-10 and soluble Fas ligand (sFasL) in the supernatant were measured by ELISA.

Results: When compared with age-matched control subjects, the level of IFN-alpha protein was significantly lower in the asthmatic youth group. The levels of IL-6, TNF-alpha, IL-10 and sFASL proteins were significantly lower in both the asthmatic youth and adult groups. Such impaired responses were not found in healthy adults with a history of childhood asthma. No significantly different responses were found between the asthmatic and control young children groups, whereas young asthmatic children with persistent wheeze after 2 years of follow-up showed significantly lower IL-10 production than those without persistent wheeze.

Conclusions: Impaired production of both anti-viral and inflammatory cytokines by PBMCs upon RV stimulation may be involved in the higher susceptibility to RV infection that is seen in asthmatic patients. In addition, such immune responses–especially regulatory cytokine production–may play important roles in the development or disappearance of persistent wheeze in children with asthma.