Anti-inflammatory effect of low intensity ultrasound (LIUS) on complete Freund's adjuvant-induced arthritis synovium

Abstract

Arthritis with intra-articular inflammation was accompanied by joint pain, swelling, and stiffness leading to significant functional impairment. Thus, regulation of joint inflammation is a good therapeutic approach for patients with arthritis. In this study, the effect of low intensity ultrasound (LIUS) applied to an adjuvant-induced arthritic rat model on the synovium was investigated. Synovial inflammation was induced by complete Freund's adjuvant (CFA)-injection into the rat knee joint. LIUS (200mW/cm(2)) was applied on the ipsilateral knee everyday for 10min beginning 1day after inflammation induction. The expression of proinflammatory factors and immunohistochemical staining pattern of the synovium were assessed. CFA induced an increase of the knee circumference that was significantly diminished by LIUS. Synovial membrane hyperplasia in the ipsilateral joint was also affected by LIUS. The inflammatory mediators, COX-1/2, IL-1β, and iNOS, but not TNF-α, in the synovial membrane were induced after 3days, and they closely correlated with the degree of edema. In the synovial membrane, the expression of inflammatory mediators was reduced by LIUS. The chemoattractant chemokine receptor CCR5 also was involved. On immunohistochemical analysis, CFA caused increased infiltration of CD11b-positive cells in the synovium. After 3days, neutrophils, myeloperoxidase (MPO)-positive cells filled the inflammatory core; later, monocytes and macrophages, ionized calcium binding adaptor molecule 1 (Iba1)-positive cells in the periphery infiltrated the core by day 5. LIUS markedly reduced CFA-induced inflammatory cells infiltration. LIUS showed a potent anti-inflammatory effect in this animal arthritis model with reduced infiltration of inflammatory cells into the synovium.