Allergic airway inflammation: unravelling the relationship between IL-37, IL-18Rα and Tir8/SIGIRR

Abstract

The hallmarks of allergic bronchial asthma arise from chronic airway inflammation. Thus, elucidating the mechanisms regulating the maintenance of this chronic inflammatory response is key to understanding asthma pathogenesis. To date, it is not clear whether a predominance of proinflammatory factors or a reduced capacity of counterbalancing anti-inflammatory mediators is the pivotal factor predisposing individuals towards asthma development. The IL-1 cytokine family and its receptor systems comprise a variety of proinflammatory cytokines like IL-1β and IL-18 and anti-inflammatory molecules such as the Toll/interleukin-1 receptor 8/single Ig IL-1 receptor (IL-R)-related molecule (Tir8/SIGIRR) and the recently established cytokine IL-37. This article reviews the functions of these IL-1 cytokine family members in the regulation of allergic airway inflammation and asthma as they have been assessed clinically, in vitro and in mouse models.

Keywords:

• asthma
• chronic inflammation
• regulation
• IL-37
• IL-18Rα
• Tir8/SIGIRR
• TH2 cells
• inflammasome
• caspase-1

Key issues

• Allergic bronchial asthma arises from a chronic inflammatory response in the airways.

• IL-37 is a cytokine with the capacity to regulate innate and adaptive immune responses by decreasing the production of proinflammatory cytokines.

• Children with allergic bronchial asthma reveal reduced expression of IL-37.

• IL-37 requires IL-18Rα and Tir8/SIGIRR to evolve its regulatory functions.

• IL-37 interferes with the inflammasome complex.

• Exogenous administration of IL-37 provides beneficial effects in mouse models of inflammatory disorders such as allergic bronchial asthma.

• Further research is required to decipher the molecular mode of action of IL-37.

• IL-37 supplementation as a novel treatment option for chronic inflammatory diseases such as asthma.

Financial & competing interests disclosure

The work was supported by the German Center for Lung Research (DZL AA2.1). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.