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

Authors
V Fattori, L Staurengo-Ferrari, TH Zaninelli et al

Lab
Laboratory of Pain, Inflammation, Neuropathy, and Cancer, Department of Pathology, Londrina State University, Londrina, Brazil

Journal
Inflammation Research

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-1beta and superoxide anion levels. In macrophages, IL-33 enhanced the release of IL-1beta 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.

BIOSEB Instruments Used:
Static Weight Bearing Touch: Incapacitance Test (BIO-SWB-TOUCH-M)