Background: Rheumatoid arthritis (RA) is characterized by endothelial activation (EA), endothelial dysfunction and vascular inflammation, leading to accelerated atherosclerosis. In the last decade, a renewed interest in cryotherapy - local or whole body - has emerged. Although growing evidence demonstrated that ice cryotherapy reduces not only pain but also disease progression, whether such therapy might blunt disorders of the systemic vasculature is unknown.

Objectives: The aim of our study was to determine the effects of a subchronic treatment with ice cryotherapy on aortic leucocyte infiltration and markers of endothelial activation in the rat adjuvant-induced arthritis (AIA) model.

Methods: AIA was induced by injection of Mycobacterium butyricum in Freund’s incomplete adjuvant at the base of the tail in 6-week-old male Lewis rats. AIA rats were treated or not with ice applied on paws, from the onset of arthritis to the acute inflammatory stage of the disease, twice a day for 14 days. Arthritis score and paw skin temperature were daily monitored. At the end of the treatment, leucocyte infiltration and the different cell subsets (monocytes/macrophages, neutrophils, CD4 ⁺ and CD8 ⁺ T cells producing or not IL-17A) were measured in thoracic aorta using flow cytometry. Relative mRNA expression of cytokines/chemokines (IL-6, TNF-α, CXCL-1, MIP-1α (CCL-3), MCP-1 (CCL-2)) and adhesion molecules (ICAM-1, VCAM-1) was analyzed in thoracic aorta by RT-qPCR. X-Ray analysis of hind paws was performed to assign a radiographic score.

Results: Treatment with ice cryotherapy, that decreased skin surface temperature from 28.6 ± 0.3°C to 18.5 ± 0.2°C, reduced arthritis score (-36%, p<0.001) and radiographic score (-34%, p<0.05) with a positive effect on osteoporosis, cartilage and bone destruction. These effects were associated with a dramatic decrease in CD4 ⁺ , CD8 ⁺ and Tc17 cell aortic infiltration as compared to untreated AIA. By contrast, ice had no effect on endothelial activation markers except VCAM-1 mRNA expression that was significantly increased (p<0.05). A positive correlation was found between the number of total leucocytes, monocytes/macrophages, CD4 ⁺ and CD8 ⁺ T cells in aorta and arthritis score.

Conclusion: In the model of AIA that reproduces arterial wall inflammation recently characterized in rheumatoid arthritis by PET/CT [1], local ice cryotherapy exerts not only local beneficial effects on the joints but also systemic benefits on vascular inflammation in large vessels. These results suggest that reduction of vascular comorbidities might be a new output of ice cryotherapy used as an adjunctive therapy in RA.

REFERENCES:

[1]Agca et al. Rheumatology (Oxford ) (2021)

Disclosure of Interests: None declared.