title: IL-33 neutralization suppresses lupus disease in lupus-prone mice.
abstract: IL-33 is a new member of the IL-1 family that plays a role in inflammation. In this study, we evaluated the potential of IL-33 inhibition as a treatment for systemic lupus erythematosus (SLE) using the lupus-prone model MRL/lpr mice and the underlying mechanisms of action. We treated mice with anti-mouse IL-33 antibody (anti-IL-33Ab) via intraperitoneal injection every other day from week 14 until week 20 for 6 weeks. A control group received the same amount of IgG control. Renal damage and mouse survival were compared. Cytokines, antibodies, immune complex, Tregs, myeloid-derived suppressor cells (MDSCs), and Th17 cells were also analyzed. Correlations between serum IL-33 and SLE disease activity index in human SLE were also investigated. MRL/lpr mice treated with anti-IL-33Ab showed reduced proteinuria and reduced serum anti-dsDNA levels. Nephritis, immune complex deposits, and the circulating antibodies and immune complex besides the mortality were significantly reduced by anti-IL-33Ab. Anti-IL-33Ab remarkably increased Tregs and MDSCs and reduced the Th17 cells and IL-1β, IL-6, and IL-17 levels in MRL/lpr mice. These results suggest that IL-33 inhibition may inhibit SLE via expansion of Tregs and MDSCs and inhibition of Th17 cells and proinflammatory responses, indicating that blockade of IL-33 has a protective effect on SLE.
authors.affiliation: Institute of Immunology of Fujian Union Hospital Affiliated to Fujian Medical University, Fuzhou, China.
authors.forename: Pin
authors.initials: P
authors.lastname: Li
authors.forename: Wei
authors.initials: W
authors.lastname: Lin
authors.forename: Xiangxiong
authors.initials: X
authors.lastname: Zheng
mesh_terms: D000818:Animals; D000906:Antibodies / Q000097:blood / Q000494:pharmacology*; D000974:Antibodies, Antinuclear / Q000097:blood; D000936:Antigen-Antibody Complex / Q000097:blood; D003176:Complement C3 / Q000276:immunology; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D007105:Immune Complex Diseases / Q000188:drug therapy; D007074:Immunoglobulin G / Q000276:immunology; D007249:Inflammation / Q000276:immunology; D020381:Interleukin-17 / Q000097:blood; D053583:Interleukin-1beta / Q000097:blood; D000067596:Interleukin-33; D015850:Interleukin-6 / Q000097:blood; D007378:Interleukins / Q000037:antagonists & inhibitors* / Q000097:blood / Q000276:immunology; D007668:Kidney / Q000293:injuries; D008180:Lupus Erythematosus, Systemic / Q000276:immunology* / Q000401:mortality; D008181:Lupus Nephritis / Q000188:drug therapy; D051379:Mice; D022423:Myeloid Cells / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D058504:Th17 Cells / Q000276:immunology
chemical_list: D000906:Antibodies; D000974:Antibodies, Antinuclear; D000936:Antigen-Antibody Complex; D003176:Complement C3; C587672:IL1B protein, mouse; C506535:Il33 protein, mouse; D007074:Immunoglobulin G; D020381:Interleukin-17; D053583:Interleukin-1beta; D000067596:Interleukin-33; D015850:Interleukin-6; D007378:Interleukins