Abstract
BackgroundIn response to viral infection, bronchial epithelial cells increase inflammatory cytokine release to activate the immune response and curtail viral replication. In atopic asthma, enhanced expression of Th2 cytokines is observed and we postulated that Th2 cytokines may augment the effects of rhinovirus-induced inflammation.MethodsPrimary bronchial epithelial cell cultures from pediatric subjects were treated with Th2 cytokines for 24 h before infection with RV16. Release of IL-8, IP-10 and GM-CSF was measured by ELISA. Infection was quantified using RTqPCR and TCID50. Phosphatidyl inositol 3-kinase (PI3K) and P38 mitogen activated protein kinase (MAPK) inhibitors and dexamethasone were used to investigate differences in signaling pathways.ResultsThe presence of Th2 cytokines did not affect RV replication or viral titre, yet there was a synergistic increase in IP-10 release from virally infected cells in the presence of Th2 cytokines. Release of IL-8 and GM-CSF was also augmented. IP-10 release was blocked by a PI3K inhibitor and IL-8 by dexamethasone.ConclusionTh2 cytokines increase release of inflammatory cytokines in the presence of rhinovirus infection. This increase is independent of effects of virus replication. Inhibition of the PI3K pathway inhibits IP-10 expression.
Highlights
Asthma is a complex respiratory disease characterized by variable airflow obstruction, bronchial hyper-responsiveness and airway inflammation
Th2 cytokines enhance RV16-induced IP-10 release Upregulation of IL-8 expression by IL-13 (10 ng/ml) and IL-4 (10 ng/ml) treatment was confirmed by ELISA
Initial experiments showed cultures treated with IL-4, IL-13 or both cytokines released significantly higher amounts of IL-8 than no treatment (NT) controls (p,0.001, Figure 1A, n = 9) but there was no difference between treatments
Summary
Asthma is a complex respiratory disease characterized by variable airflow obstruction, bronchial hyper-responsiveness and airway inflammation. The Th2 type cytokines interleukin (IL)-13 and IL-4 [1] are key players in allergic responses, playing a pivotal role in inflammatory and remodelling aspects of asthma pathogenesis [2,3]. Th2 cytokines can impair immune responses to viral infections. A combination of sensitization, high exposure to one or more allergens, and viral detection significantly increases the risk of hospitalization for asthma [11,12]. In response to viral infection, bronchial epithelial cells increase inflammatory cytokine release to activate the immune response and curtail viral replication. In atopic asthma, enhanced expression of Th2 cytokines is observed and we postulated that Th2 cytokines may augment the effects of rhinovirus-induced inflammation
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