IL37 relieves allergic inflammation by inhibiting the CCL11 signaling pathway in a mouse model of allergic rhinitis

Allergic rhinitis (AR) is the allergic inflammation of immune cells in the nasal mucosa, caused by an abnormal Tcell response. Interleukin (IL)37, a unique member of the IL1 family with broad antiinflammatory roles in various autoimmune diseases, participates in the immune regulation of AR. However, the regulatory mechanism of IL37 in AR has remained elusive. In the present study, a mouse model of AR was established by treating mice with ovalbumin (OVA). Following systemic administration of IL37, the effects of the cytokine on allergic symptoms were evaluated. The nasal mucosal infiltration of eosinophils was assessed by histopathological observation. The serum and nasal lavage fluid concentrations of immunoglobulin (Ig)E, IgG1, IgG2a, interferon (IFN)γ, IL4, IL13, IL17a and CC motif cytokine ligand (CCL)11 were determined by ELISA. Treatment with OVA resulted in allergic symptoms, including enhanced eosinophil infiltration in the nasal mucosa, increased thickness of the nasal mucosa and increased levels of IgE, IgG1, IgG2a, IL4, IL13, IL17a and CCL11, but the level of IFNγ was indicated to decrease. After IL37 treatment, the frequency of nasal rubbing and sneezing was reduced compared with that in the OVA group. IL37 administration also decreased the number of eosinophils in the nasal mucosa and the thickness of the nasal mucosa, as well as the serum and nasal lavage fluid levels of IgE, IgG1, IgG2a, IL4, IL13, IL17a and CCL11, but the level of IFNγ decreased. In addition, the OVAinduced increases in histamine and substance P levels were reversed by IL37 administration. CCL11 expression levels were correlated with the expression levels of IFNγ, IL4, IL13, IL17a, histamine and substance P. In conclusion, IL37 alleviated the OVAinduced allergic symptoms and allergic inflammatory response by reducing the serum cytokine levels via decreasing CCL11 expression levels in mice.