IL‑37 relieves allergic inflammation by inhibiting the CCL11 signaling pathway in a mouse model of allergic rhinitis

Abstract

Allergic rhinitis (AR) is the allergic inflammation of immune cells in the nasal mucosa, caused by an abnormal T-cell response. Interleukin (IL)-37, a unique member of the IL-1 family with broad anti-inflammatory roles in various autoimmune diseases, participates in the immune regulation of AR. However, the regulatory mechanism of IL-37 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 IL-37, 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, IL-4, IL-13, IL-17a 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, IL-4, IL-13, IL-17a and CCL11, but the level of IFN-γ was indicated to decrease. After IL-37 treatment, the frequency of nasal rubbing and sneezing was reduced compared with that in the OVA group. IL-37 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, IL-4, IL-13, IL-17a and CCL11, but the level of IFN-γ decreased. In addition, the OVA-induced increases in histamine and substance P levels were reversed by IL-37 administration. CCL11 expression levels were correlated with the expression levels of IFN-γ, IL-4, IL-13, IL-17a, histamine and substance P. In conclusion, IL-37 alleviated the OVA-induced allergic symptoms and allergic inflammatory response by reducing the serum cytokine levels via decreasing CCL11 expression levels in mice.

The Role of Macrophages in the Development of Acute and Chronic Inflammatory Lung Diseases

“…Interestingly, the suppression of these signaling pathways has led to amelioration of the symptoms of allergic asthma via inhibition of inflammatory cell recruitment, cytokine production, and mucus hypersecretion in both OVA- and HDMs-induced experimental animal models. Recently, Lei et al showed that IL-37 administration exerts an ameliorative effect on OVA-induced allergic asthma mice by suppressing the levels of eosinophil numbers and the generation of IL-4, IL-13, IL-17, CCL11, and histamine [ 114 ].…”

“…COPD is characterized by chronic bronchitis, oxidative stress, mucus hypersecretion, emphysema, and persistent airflow limitation [ 41 , 116 , 117 , 118 ]. Cigarette smoking is known to be the greatest risk factor for COPD [ 113 , 114 , 115 ]. Guiedem et al reported that respiratory infection makes breathing much more difficult and leads to further lung damage in the pathogenesis of COPD [ 118 ].…”

Comparative Transcriptomic Analysis Reveals the Immunosuppressive Targets of Mesalazine in Dextran Sulfate Sodium-Induced Ulcerative Colitis

“…CCL11 expression levels correlated with the expression levels of different ILs. Reduced expression of CCL11 has been reported to alleviate allergic symptoms and allergic inflammatory responses by reducing serum cytokine levels ( Lei et al, 2020 ). It has been reported that CD4+ CD25+ T cells inhibit the development of colitis induced by both Th1 and Th2 cells in a mouse model ( Xu et al, 2003 ).…”

Total glucosides of paeony ameliorates oxidative stress, apoptosis and inflammatory response by regulating the Smad7‑TGF‑β pathway in allergic rhinitis

“…Adrenoreceptor β2 inhibits AR inflammatory cytokine production induced by IL-13 ( 45 ). IL-37 suppresses the C-C motif chemokine ligand 11 signaling pathway to alleviate allergic inflammation in AR mice ( 46 ). The present study verified that TGP ameliorated the inflammatory response in AR mice by decreasing IL-4, IL-5, IL-17 and IFN-γ levels.…”