Local ice cryotherapy reduced vascular inflammation in large artery from rats with arthritis

Rheumatoid arthritis (RA) is associated with increased cardiovascular risk, prompting the exploration of adjunctive therapies to mitigate vascular complications. This study investigated the vascular effects of local ice cryotherapy in the adjuvant-induced arthritis (AIA) rat model, with a focus on vascular inflammation, immune cell infiltration, and arthritis severity. AIA rats received local ice application twice daily to inflamed joints for 14 days. Arthritis severity and joint damage were assessed clinically and radiographically. Aortic mRNA expression of endothelial activation (CXCL-1, CCL-2, CCL-3, ICAM-1, VCAM-1) and dysfunction markers (COX-2, Arginase-2, p22 and p47phox) were assessed by RT-qPCR. Circulating and aortic leukocyte populations (including CD4⁺, CD8⁺, Tc17, Th17 T lymphocytes, neutrophils and monocytes) were determined by flow cytometry. Plasma levels of sclerostin (SOST) and osteoprotegerin (OPG) were measured using Multiplex. Ice cryotherapy significantly reduced arthritis severity and joint damage, decreased aortic COX-2 and p47phox expression, but increased VCAM-1 expression, and markedly reduced aortic infiltration by CD4⁺, CD8⁺ T cells, and Tc17 cells, without affecting circulating leukocyte counts or plasma OPG and SOST. Decrease in arthritis score correlated positively with reduced vascular immune infiltration. These findings suggest potential anti-inflammatory and vasculoprotective benefits from local ice cryotherapy, supporting its use as a well-tolerated RA adjunct therapy.