Interleukin- 33 (IL-33) is an epithelial-derived cytokine that initiates type 2 immune responses to allergens, though whether IL-33 has the ability to modify responses to respiratory viral infections remains unclear. This study aimed to investigate the effects of IL-33 on rhinovirus (RV)-induced immune responses by circulating leukocytes from people with allergic asthma, and how this response may differ from non-allergic controls. Our experimental approach involved co-exposing peripheral blood mononuclear cells to IL-33 and RV in order to model how the functions of virus-responsive lymphocytes could be modified after recruitment to an airway environment enriched in IL-33. In the current study, IL-33 enhanced RV-induced IL-5 and IL-13 release by cells from people with allergic asthma, but had no effect on IL-5 and IL-13 production by cells from healthy donors. In asthmatic individuals, IL-33 also enhanced mRNA and surface protein expression of ST2 (the IL-33 receptor IL1RL1), while soluble ST2 concentrations were low. In contrast, IL-33 had no effect on mRNA and surface expression of ST2 in healthy individuals. In people with allergic asthma, RV-activated ST2+ innate lymphoid cells (ST2+ILC) were the predominant source of IL-33 augmented IL-13 release. In contrast, RV-activated natural killer cells (NK cells) were the predominant source of IL-33 augmented IFNγ release in healthy individuals. This suggests that the effects of IL-33 on the cellular immune response to RV differ between asthmatic and healthy individuals. These findings provide a mechanism by which RV infections and IL-33 might interact in asthmatic individuals to exacerbate type 2 immune responses and allergic airway inflammation.

While there has been much interest in using biomarkers to select patients for particular targeted therapies, there has been much less attention paid to how these biomarkers change in patients once treatment begins. This is an area of great interest to practising clinicians, especially respiratory physicians and allergists who manage severe asthma. In this article, we review monoclonal antibodies and related targeted therapies, especially those that are currently available or in late stage clinical trials, focussing on the differential effects such agents have on biomarkers in widespread clinical practice such as eosinophils, FeNO and total IgE. Serial measurements of biomarkers can be useful in determining whether a particular targeted therapy is having its expected biological effect and invaluable in assessing the reasons for treatment failure should that occur.

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