Blocking Interleukin-33 Alleviates the Joint Inflammation and Inhibits the Development of Collagen-Induced Arthritis in Mice.

Yan Li,Mingcai Li,Huan Chen,Yeqin Fu,Yan Yang,Xiaojin Liu

doi:10.1155/2020/4297354

Abstract

Rheumatoid arthritis (RA) is considered a systemic chronic inflammatory joint disease characterized by chronic synovitis and cartilage and bone destruction. Interleukin-33 (IL-33) is a proinflammatory cytokine which is highly expressed in the synovium of RA patients and the joints of mice with collagen-induced arthritis (CIA) and exacerbates CIA in mice. However, the role of the IL-33-neutralizing antibody in the murine model of CIA remains unclear. In the present study, CIA mice were given intraperitoneally with polyclonal rabbit anti-murine IL-33 antibody (anti-IL-33) or normal rabbit IgG control after the first signs of arthritis. Administration of anti-IL-33 after the onset of disease significantly reduced the severity of CIA and joint damage compared with controls treated with normal rabbit IgG. Anti-IL-33 treatment also significantly decreased the serum levels of interferon-γ(IFN-γ),IL-6, IL-12, IL-33, and tumor necrosis factor-α (TNF-α). Moreover, anti-IL-33 treatment significantly downregulated the production of IFN-γ, IL-6, IL-12, IL-33, and TNF-α in ex vivo-stimulated spleen cells. Together, our results indicate that the IL-33-neutralizing antibody may provide a therapeutic strategy for RA by inhibiting the release of proinflammatory cytokines.

Highlights

Interleukin-33 (IL-33) is a new member of the IL-1 family, which plays a biological role by binding the orphan receptor suppression of tumorigenicity 2 (ST2) [1]
The results showed that mice injected with control rabbit IgG reached the peak of arthritis on day 29
We demonstrated that anti-IL-33 can reduce the severity of arthritis and the signs of joint injury in collagen-induced arthritis (CIA) mice after the onset of arthritis

Summary

Introduction

Interleukin-33 (IL-33) is a new member of the IL-1 family, which plays a biological role by binding the orphan receptor suppression of tumorigenicity 2 (ST2) ( called ST2L, IL33Rα, DER4, Fit-1, T1, IL-1RL1, or IL-1R4) [1]. Upon binding to IL-33, the ST2 receptor together with the IL-1 receptor accessory protein (IL-1RAcP) forms a functional signaling heterodimeric complex [1]. IL-33 can activate nuclear factor-κB (NF-κB) and mitogen-activated protein kinases (MAPK) through binding with ST2 receptor and induce Th2 cytokine expression, leading to serious pathological changes in mucosal tissues [1]. IL-33 has many effects on inflammatory cells It can induce mast cells and Th2 cells to produce proinflammatory and Th2 cytokines [1, 5,6,7,8,9,10,11], induce Th2 cell chemotaxis [12] and neutrophil migration [13], promote eosinophil and basophil adhesion, and enhance eosinophil survival and basophil migration [14,15,16]. IL-33 is involved in the pathogenesis of rheumatoid arthritis (RA) [17]

Methods

Results

Conclusion