Interleukin-25 is upregulated in patients with systemic lupus erythematosus and ameliorates murine lupus by inhibiting inflammatory cytokine production

• Published in: International immunopharmacology Vol. 74; p. 105680
• Main Authors: Li, Yongsheng, Wang, Rui, Liu, Shanshan, Liu, Juan, Pan, Wenyou, Li, Fang, Li, Ju, Meng, Deqian
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01-09-2019; Elsevier BV
• Subjects: Adult; Animals; Anti-DNA antibodies; Autoimmune diseases; Cells, Cultured; Chronic conditions; Cytokines; Cytokines - metabolism; Diagnostic systems; Disease activity; Disease Models, Animal; Female; Humans; IL-1β; Immunoglobulin G; In vivo methods and tests; Inflammation Mediators - metabolism; Inflammatory cytokine; Inflammatory diseases; Interleukin 12; Interleukin 17; Interleukin 6; Interleukin-17 - metabolism; Interleukin-25; Interleukins - metabolism; Leukocytes (mononuclear); Lupus; Lupus Erythematosus, Systemic - immunology; Lupus Nephritis - immunology; Male; Mice; Mice, Inbred MRL lpr; Middle Aged; mRNA; Pathogenesis; Patients; Peripheral blood mononuclear cells; Serum levels; Signs and symptoms; Systemic lupus erythematosus; Therapeutic applications; Tumor necrosis factor-α; Up-Regulation; Young Adult; β-Interferon; γ-Interferon; Interleukin-25; Systemic lupus erythematosus; Disease activity; Inflammatory cytokine
• ISSN: 1567-5769; 1878-1705
• DOI: 10.1016/j.intimp.2019.105680

Interleukin-25 (IL-25), an anti-inflammatory member of the IL-17 family of cytokines, has been extensively investigated in multiple autoimmune and inflammatory diseases. However, its pathogenic role in systemic lupus erythematosus (SLE) remains largely unknown. This study aimed to explore the expression and clinical significance of IL-25 in patients with SLE as well as its pathogenic role in lupus-prone MRL/lpr mice. The results showed that IL-25 mRNA and serum levels were increased in patients with SLE compared with those in healthy controls. Higher IL-25 mRNA and serum levels were found in patients with an active disease. IL-25 levels were positively associated with SLEDAI, anti-dsDNA, and IgG but negatively associated with C3 and C4. Ex vivo assay showed that IL-25 could inhibit the production of the inflammatory cytokines IL-1β, IL-17, IL-6, and IFN-γ as well as TNF-α in the peripheral blood mononuclear cells in patients with SLE. In vivo studies revealed that treatment with IL-25 significantly ameliorated lupus symptoms in lupus-prone MRL/lpr mice by suppressing the production of inflammatory cytokines, including IL-1α, IL-1β, IL-6, IL-12p70, IL-17A, and IFN-β. Cumulatively, our results suggest that IL-25 levels are increased in patients with SLE and associated with disease activity; IL-25 plays a potent immunosuppressive role in the pathogenesis of SLE by suppressing the production of inflammatory cytokines. IL-25 could potentially be used as a diagnostic and therapeutic target for SLE treatment.
•IL-25 mRNA and serum levels are upregulated in patients with SLE and associated with disease severity.•Serum IL-25 levels are associated with inflammatory cytokines in SLE patients.•IL-25 inhibits inflammatory cytokines production in PBMCs of SLE patient.