Elevated synovial fluid levels of interleukin‐6 and tumor necrosis factor associated with early experimental canine osteoarthritis

Abstract

Objective. To measure levels of cytokines, proteases, and glycosaminoglycans (GAG) in synovial fluid (SF) From the knees of animals with experimental osteoarthritis (OA) and from their contralateral (control) knees, and to compare and correlate these values with each other as well as with measures of proteoglycan synthesis in the corresponding articular cartilage. This study will help to identify cytokines of potential importance in the early stages of the development of OA.Methods. OA was induced in 12 mature animals by sectioning the anterior cruciate ligament. After 3 months, SF From the operated and contralateral (control) knee joints was assayed for interleukind (IL-6), tumor necrosis Factor (TNF), IL-1, latent metalloproteinase, and sulfated GAG. Proteoglycan synthesis in the corresponding articular cartilage was also measured.Results. IL-6 levels in SF from the operated joint compared with the control joint were significantly ele- Submitted for publication July 9, 1992; accepted in revised form January 6, 1993. vated in 11 of 12 animals. TNF levels were also elevated in 10 of 11 SF samples from operated joints, but to a lesser extent than those of IL-6. IL-1 and IL-1 inhibitors were undetectable in either the operated or control joint SF. The GAG concentration was elevated in SF from experimental OA joints. This elevation correlated with that of TNF, but not IL-6. There was no significant difference in the concentration of APMA-activatable metalloproteinase. The rate of proteoglycan synthesis was higher in the cartilage from the operated joint in 8 of 12 animals, and the mean rate of synthesis was significantly higher than in the control joint. There was a positive correlation between this increase in cartilage proteoglycan synthesis (operated versus control) and the increase in SF IL-6, but there was no correlation with the levels of TNF or GAG.Conclusion. This is the first study of SF levels of cytokines in early experimental OA. Our results show surprisingly high levels of IL-6 in operated joints, where the cytokine could act directly on the chondrocytes, and thus play a role in mediating their responses to cartilage injury.

Effects of tenidap on canine experimental osteoarthritis i. morphologic and metalloprotease analysis

“…There are several possible mechanisms that may be involved in increasing MMP synthesis in this OA model. The prime candidates are cytokines such as IL-1 and TNFa, since an increased level of IL-la and IL-1 p was demonstrated in OA synovium and cartilage in this model (9, associated with an increased level of TNFa in the synovial fluid (11). This hypothesis is strengthened by a recent report indicating that intraarticular injections of dog monocyte-conditioned medium into the knee joint of dogs increase the expression of the MMPs collagenase and stromelysin, in both synovium and cartilage in vivo (59).…”

Interleukin‐17 up‐regulation of nitric oxide production in human osteoarthritis cartilage

“…IL-17 up-regulates cytokines such as IL-6, G-CSF, and IL-8 in synovial cells (9). These cytokines have been detected in OA and RA synovial fluids and are reported to be released also by chondrocytes (10)(11)(12). It is tempting to speculate that the role of IL-17 in inflammatory arthropathies such as RA may be more pronounced because the infiltrated T cells in the joints releasing IL-17 may not only up-regulate other cytokines in the joints, but may also directly up-regulate NO production in the cartilage.…”

Immunopathological mechanisms in dogs with rupture of the cranial cruciate ligament

“…These studies provide evidence that TNF-a contributes to the pathogenesis of these diseases, even in the chronic stages. In dogs with RA, spontaneous CrCL rupture and experimentally transected CrCL, TNF-a bioactivity in the SF varied from undetectable to elevated (Carter et al, 1999;Venn et al, 1993;Fujita et al, 2006;Hay et al, 1997). Recently, TNF-a mRNA expression has been detected in SF cells from dogs with immune-mediated arthritides and spontaneous CrCL rupture, with higher levels in the immune-mediated group (Hegemann et al, 2005).…”

“…Cytokine studies of dogs with various arthropathies also implicate IL-6 as a general indicator of joint inflammation. Dogs with natural occurring and experimentally induced CrCL rupture have higher IL-6 bioactivity in their SF compared with healthy dogs (Carter et al, 1999;Venn et al, 1993;Fujita et al, 2006;Hay et al, 1997), SF of dogs with CRA have significant higher IL-6 bioactivity than dogs with natural occurring CrCL rupture (Carter et al, 1999). Higher IL-6 gene expression is also detected in SF cells from dogs with immune-mediated polyarthritis compared with that from dogs with natural occurring CrCL rupture (Hegemann et al, 2005).…”