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IL-33 Neutralization Suppresses Lupus Disease in Lupus-Prone Mice

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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.

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Authors and Affiliations

  1. Institute of Immunology of Fujian Union Hospital Affiliated to Fujian Medical University, Fuzhou, China

    Pin Li

  2. Cadre’s Ward, Fujian Union Hospital Affiliated to Fujian Medical University, Fuzhou, China

    Wei Lin

  3. Department of Rheumatology, Fujian Union Hospital Affiliated To Fujian Medical University, 29 Xinquan Road, Fuzhou, 350001, Fujian, China

    Xiangxiong Zheng

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Correspondence to Xiangxiong Zheng.

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Li, P., Lin, W. & Zheng, X. IL-33 Neutralization Suppresses Lupus Disease in Lupus-Prone Mice. Inflammation 37, 824–832 (2014). https://doi.org/10.1007/s10753-013-9802-0

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