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

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

• Authors: Victor Fattori, Larissa Staurengo-Ferrari, Tiago H Zaninelli, Rubia Casagrande, Rene D Oliveira, Paulo Louzada-Junior, Thiago M Cunha, Jose C Alves-Filho, Mauro M Teixeira, Fernando Q Cunha, Flavio A Amaral, Waldiceu A Verri Jr
• Journal: Inflammation research : official journal of the European Histamine Research Society ... [et al.] (Inflamm Res) Vol. 69 Issue 12 Pg. 1271-1282 (Dec 2020) ISSN: 1420-908X [Electronic] Switzerland
• PMID: 32886146 (Publication Type: Journal Article)

Chemical References

• IL1B protein, mouse
• IL33 protein, human
• Il1rl1 protein, mouse
• Interleukin-1 Receptor-Like 1 Protein
• Interleukin-1beta
• Interleukin-33
• Superoxides
• Uric Acid
• Peroxidase

Topics

• Animals
• Arthritis, Gouty (chemically induced, metabolism, pathology)
• Female
• Humans
• Inflammation (chemically induced, psychology)
• Interleukin-1 Receptor-Like 1 Protein (genetics)
• Interleukin-1beta (metabolism)
• Interleukin-33 (pharmacology)
• Macrophages (drug effects, metabolism)
• Male
• Mice
• Mice, Inbred BALB C
• Mice, Knockout
• Middle Aged
• Neutrophil Infiltration (drug effects)
• Pain (chemically induced, psychology)
• Peroxidase (metabolism)
• Superoxides (metabolism)
• Synovial Membrane (pathology)
• Uric Acid