Background/Purpose: Little is known regarding the potential benefits of exercise on managing acute gout. Consequently, recent clinical practice guidelines released by the American College of Rheumatology (2012) and the American College of Physicians (2016) contain no recommendations regarding exercise in gout patients. Currently, many rheumatologists recommend resting the involved joints during an acute attack based on animal studies performed nearly a half century ago. Since the potential for exercise to suppress gouty inflammation is an area of study that has yet to be researched sufficiently, the aim of this study was to determine the efficacy of exercise in an acute mouse model.

Methods: BALB/C-Tg(NFκB-RE-luc)-Xen mice, which contain a firefly luciferase cDNA reporter gene under the regulation of NFκB, were exercised by daily treadmill walking (45 min/day for 2 weeks) at low intensity (35% VO₂max; 8 m/min), moderate intensity (55% VO₂max; 11 m/min), and high intensity (75% VO₂max; 15 m/min). At the end of the 2 week conditioning period, monosodium urate (MSU) crystal-induced arthritis was induced by intra-articular injection of MSU (0.5 mg) into the tibio-tarsal joint (ankle) under anesthesia. Localized NFκB activity was measured using the Xenogen in vivo imaging system (IVIS 200). Serum was collected to measure cytokine expression and tissue was collected for histological analysis. 

Results: Histopathology of feet/ankle regions demonstrated a decrease in cellular infiltrate into the joint spaces by H&E staining and a marked decrease in macrophage and neutrophils, as indicated by immunohistochemistry and quantification in mice exercised at low intensity (8 m/min) when compared to non-exercised controls. Low intensity exercise also significantly suppressed serum expression of IL-12, KC/GRO, TNF-α, and IL-6 in MSU-induced gout mice relative to non-exercised and wild-type controls. Caliper measurements of foot pads revealed a significant reduction in swelling with both low and moderate exercise when compared to non-exercised controls, while no difference was observed with high intensity exercise. Additionally, IVIS measurements of the injected ankles demonstrated that NFκB activity was significantly reduced with low and moderate exercise, but slightly elevated following the high intensity regimen relative to non-exercised control mice.

Conclusion: Our results from an acute gout mouse model suggest that low and moderate exercise may be effective in decreasing gouty inflammation. Thus, these data could support a change in the conventional exercise recommendations provided by Rheumatologists in gout patients. Further studies are needed to more comprehensively evaluate this potentially important observation and to elucidate the mechanism responsible for this observation.