IL-33 enhances macrophage release of IL-1 beta and promotes pain and inflammation in gouty arthritis

Author(s):Show less -

Fattori, Victor ^[1] ; Staurengo-Ferrari, Larissa ^[1] ; Zaninelli, Tiago H. ^[1] ; Casagrande, Rubia ^[2] ; Oliveira, Rene D. ^[3] ; Louzada-Junior, Paulo ^[3] ; Cunha, Thiago M. ^[4] ; Alves-Filho, Jose C. ^[4] ; Teixeira, Mauro M. ^[5] ; Cunha, Fernando Q. ^[4] ; Amaral, Flavio A. ^[5] ; Verri Jr, Waldiceu A.

Affiliation

^[1] Univ Estadual Londrina, Dept Pathol, Lab Pain Inflammat Neuropathy & Canc, Londrina, Parana - Brazil

^[2] Univ Estadual Londrina, Dept Pharmaceut Sci, Londrina, Parana - Brazil

^[3] Univ Sao Paulo, Ribeirao Preto Med Sch, Div Clin Immunol, Ribeirao Preto - Brazil

^[4] Univ Sao Paulo, Ctr Res Inflammatory Dis, Ribeirao Preto Med Sch, Dept Pharmacol, Ribeirao Preto - Brazil

^[5] Univ Fed Minas Gerais, Inst Ciencias Biol ICB, Dept Bioquim & Imunol, Belo Horizonte, MG - Brazil

• Document type: Journal article
• Source: Inflammation Research; v. 69, n. 12 SEP 2020.
• Web of Science Citations: 0

Abstract

Objective To investigate the role of IL-33 in gouty arthritis. Material 174 Balb/c (wild-type) and 54 ST2(-/-)mice were used in this study. In vitro experiments were conducted in bone marrow-derived macrophages (BMDMs). Synovial fluid samples from gouty arthritis (n = 7) and osteoarthritis (n = 8) hospital patients were used to measure IL-33 and sST2 levels. Methods Gout was induced by injection of monosodium urate (MSU) crystals in the knee joint of mice. Pain was determined using the electronic von Frey and static weight bearing. Neutrophil recruitment was determined by H\&E staining, Rosenfeld staining slides, and MPO activity. ELISA was used for cytokine and sST2 measurement. The priming effect of IL-33 was determined in BMDM. Results Synovial fluid of gout patients showed higher IL-33 levels and neutrophil counts than osteoarthritis patients. In mice, the absence of ST2 prevented mechanical pain, knee joint edema, neutrophil recruitment to the knee joint, and lowered IL-1 beta and superoxide anion levels. In macrophages, IL-33 enhanced the release of IL-1 beta and TNF-alpha, and BMDMs from ST2(-/-)showed reduced levels of these cytokines after stimulus with MSU crystals. Conclusion IL-33 mediates gout pain and inflammation by boosting macrophages production of cytokines upon MSU crystals stimulus. (AU)

• FAPESP's process: 13/08216-2 - CRID - Center for Research in Inflammatory Diseases
• Grantee: Fernando de Queiroz Cunha
• Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC