The potential of interleukin-37 as an effective therapeutic agent in asthma

Lina Zhang, Jie Zhang, Peng Gao

Interleukin (IL)-37 belongs to the IL-1 cytokine family. It binds to IL-18Rα and recruits the orphan decoy IL-1R8. Emerging evidence shows that IL-37 is a key player in the regulation of inflammation, cellular differentiation, and proliferation. Altered IL-37 expression has been demonstrated in many inflammatory disease conditions, including asthma. In rheumatoid arthritis, IL-37 is involved in the regulation of proliferation, production of inflammatory mediators, and activation of inflammatory cells. Furthermore, this cytokine acts as a negative regulator of inflammation in inflammatory bowel disease. Similarly, IL-37 also appears to suppress allergic inflammation in asthma. In a murine model of asthma, local administration of IL-37 markedly reduced the degree of inflammatory cell infiltration and airway hyper-responsiveness. IL-37 has also been shown to be involved in a number of aspects of allergic inflammation, such as eosinophil and neutrophil recruitment, as well as inhibition of Th1/Th2/Th17 inflammatory mediators. However, the exact molecular mechanisms underlying the function of IL-37 in human asthma have yet to be fully elucidated. This review describes the current evidence regarding the role of IL-37 in the pathophysiology of asthma and evaluates both the potential of IL-37 as a biomarker for airway inflammation and a therapeutic target for the treatment of asthma.