Elevated synovial fluid IL-33 and IL-6 levels and cartilage degeneration in stage III osteonecrosis of the femoral head.

Abstract

Few studies have investigated interleukin (IL)-33 as a potential proinflammtory cytokine in the joint cavity following subchondral fracture occurring during osteonecrosis of the femoral head (ONFH). The aim of the present study was to investigate whether IL-33 and other proinflammtory cytokines, in addition to cartilage degeneration, were elevated in the joint cavity following subchondral fracture. IL-33 levels were analyzed in the plasma, synovial fluid, and bone marrow aspirate, and the levels of IL-6, IL-17, IL-1β, tumor necrosis factor (TNF)-α, matrix metallopeptidase (MMP)-13, and carboxy-terminal telopeptides of type II collagen (CTX-II) in synovial fluid were also quantitated to compare the levels of these proteins between stages II and III. Macro- and microscopic articular cartilage were evaluated and compared between stages II and III in the same patient. Moreover, immunohistochemical staining of MMP-13 and Col-II were examined. Of the 33 patients enrolled in the present study, 15 had hips in stage II and 18 had hips in stage III. IL-33 levels in all three sample types were significantly higher in stage III. Synovial fluid IL-6 and CTX-II levels were significantly higher in stage III. A clear step-off region in the weight-bearing area was macroscopically observed in the stage III femoral head. Microscopic evaluation showed symmetrical cartilage matrix deposition around the chondrocytes in the stage II articular cartilage, unlike that in stage III. Immunohistochemical staining of the stage III articular cartilage samples revealed positive MMP-13 staining in chondrocytes and decreased Col-II deposition in the matrix. The present study revealed elevated IL-33 and IL-6 levels and cartilage degeneration in stage III ONFH.