Cytokine profile in canine immune-mediated polyarthritis and osteoarthritis

Abstract

The purpose of this study was to determine the cytokine profile in 21 dogs with canine immune-mediated polyarthritis (IMA) and 15 dogs with osteoarthritis (OA) caused by cranial cruciate ligament rupture (CCLR). The mRNA expression of interleukin (IL)-1alpha, IL-1beta, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12, IL-18, interferon (IFN)-gamma, transforming growth factor (TGF)-beta, and tumour necrosis factor (TNF)-alpha were analysed in synovial fluid by semi-quantitative RT-PCR, while TNF-alpha protein was determined by L929 cytotoxicity assay. The frequency of lymphocytes was analysed using FACScan. Both disorders reveal a similar cytokine expression pattern, except for significant lower IL-1beta expression in OA. Th1 cytokines IL-2 and IFN-gamma were detected, while IL-4 was nearly absent in IMA and OA. Furthermore, the bioassay demonstrates a significantly higher production of TNF-alpha in synovial fluid of dogs with IMA, compared to dogs with OA (p < 0.05). The frequency of CD4+, CD8+ and MHC class II+ cells was relatively higher in synovial fluids compared to peripheral blood in IMA. These findings reveal that the difference between the cytokine pattern of canine IMA and OA seems to be rather quantitative than qualitative. Both joint disorders show predominance of pro-inflammatory cytokines and absence of TH2 cytokine expression, indicating the potential of IL-4 for a gene therapeutic approach.

Cyclosporine A Inhibits the mRNA Expressions of IL-2, IL-4 and IFN-.GAMMA., but not TNF-.ALPHA., in Canine Mononuclear Cells

“…It is therefore possible that TNF-α production is increased in dogs treated with CsA. TNF-α is a proinflammatory cytokine and considered to be an important effector molecule in the pathogenesis of IBD and immune-mediated polyarthritis [13,27]. Although a previous clinical study reported that CsA appeared to be effective in dogs with IBD that were refractory to steroids [1], the results of the present study indicate that CsA should be used with care for the treatment of TNF-α-mediated diseases.…”

“…A number of clinical trials have produced evidence to support the use of CsA for IBD and rheumatoid arthritis in humans [8,25]. In dogs, TNF-α has been indicated to play an important role in the pathogenesis of IBD and immune-mediated polyarthritis [13,27]. However, the effect of CsA on TNF-α mRNA expression has not been evaluated in dogs.…”

Autologous synovial fluid enhances migration of mesenchymal stem cells from synovium of osteoarthritis patients in tissue culture system

“…In previous reports, TNF a and IL-4 were also found present in osteoarthritic synovial fluid, 15,16 and they were thought to be potent fibroblast chemoattractants inducing migration. 17,18 These reports support our results that merely inhibiting TGFb did not fully reverse the increase of cell expansion in synovial fluid.…”

Evaluation of Glucosamine and Snail Mucin on the Progression of Experimental Knee Osteoarthritis in Dogs

“…These signals augment destruction, thus promoting the harmful cycle. No single cytokine is the sole mediator of joint damage, and the adverse effects are likely the result of a complex interaction of cytokines (Fernandes et al, 2002;Hegemann et al, 2005;Hulejová et al, 2007), proteolytic enzymes (Borzi et al, 2000), leukocytes (Sandell et al, 2008), synoviocytes (Villiger et al, 1992) and chondrocytes (Kuroki et al).…”