Cytokine profile in canine immune-mediated polyarthritis and osteoarthritis

N. Hegemann; A. Wondimu; B. Kohn; L. Brunnberg; M. F. G. Schmidt

doi:10.1055/s-0038-1632931

Veterinary and Comparative Orthopaedics and Traumatology, Table of Contents

Vet Comp Orthop Traumatol 2005; 18(02): 67-72
DOI: 10.1055/s-0038-1632931

Original Research

Schattauer GmbH

Cytokine profile in canine immune-mediated polyarthritis and osteoarthritis

Authors

N. Hegemann

¹Institute of Immunology and Molecular Biology, and the Clinic for Small Animals, Free University of Berlin, Germany
A. Wondimu^*

¹Institute of Immunology and Molecular Biology, and the Clinic for Small Animals, Free University of Berlin, Germany
B. Kohn

¹Institute of Immunology and Molecular Biology, and the Clinic for Small Animals, Free University of Berlin, Germany
L. Brunnberg

¹Institute of Immunology and Molecular Biology, and the Clinic for Small Animals, Free University of Berlin, Germany
M. F. G. Schmidt

¹Institute of Immunology and Molecular Biology, and the Clinic for Small Animals, Free University of Berlin, Germany

Abstract

Summary

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)-1α, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12, IL-18, interferon (IFN)-γ, transforming growth factor (TGF)-β, and tumour necrosis factor (TNF)-α were analysed in synovial fluid by semi-quantitative RT-PCR, while TNF-α 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-1β expression in OA. Th1 cytokines IL-2 and IFN-γ were detected, while IL-4 was nearly absent in IMA and OA. Furthermore, the bioassay demonstrates a significantly higher production of TNF-α 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.

Keywords

Dog - cytokine profile - immune-mediated polyarthritis - osteoarthritis

Full Text

References

References
1 Bennett D. Immune based erosive inflammatory joint disease of the dog. Canine rheumatoid arthritis. J Small Anim Pract 1987; 28: 799-820.
2 Berner B, Akca D, Jung T. et al. Analysis of Th1 and Th2 cytokines expressing CD4+ and CD8+ T cells in rheumatoid arthritis by flow cytometry. J Rheumatol 2000; 27: 1128-35.
3 Brunnberg L. Diagnosing lameness in dogs. Oxford: Blackwell Science; 2001
4 Cameron M, Buchgraber A, Passler H. et al. The natural history of the anterior cruciate ligament-deficient knee. Changes in synovial fluid cytokine and keratan sulfate concentrations. Am J Sports Med 1997; 25: 751-4.
5 Carter SD, Bell SC, Bari AS. et al. Immune complexes and rheumatoid factors in canine arthritides. Ann Rheum Dis 1989; 48: 986-91.
6 Carter SD, Barnes A, Gilmore WH. Canine rheumatoid arthritis and inflammatory cytokines. Vet Immunol Immunopathol 1999; 69: 201-14.
7 Feldmann M. Development of anti-TNF-a therapy of rheumatoid arthritis. Nat Rev Immunol 2002; 2: 364-71.
8 Fernandes JC, Martel-Pelletier J, Pelletier JE. The role of cytokines in osteoarthritis pathophysiology. Biorheology 2002; 39: 237-46.
9 Galloway RH, Lester SJ. Histopathological evaluation of canine stifle joint synovial membrane collected at the time of repair of cranial cruciate ligament rupture. JAmAnim Hosp Assoc 1995; 31: 289-94.
10 Gerli R, Lunardi C, Pizalis C. Unmasking the antiinflammatory cytokine response in rheumatoid synovitis. Rheumatol 2002; 41: 1341-5.
11 Goldring SR. Pathogenesis of bone and cartilage destruction in rheumatoid arthritis. Rheumatology. 2003; 42 (S2) 11-6.
12 Gracie JA, Forsey RJ, Chan WL. et al. Aproinflammatory role for IL-18 in rheumatoid arthritis. J Clin Invest 1999; 104: 1393-401.
13 Hay CW, Chu Q, Budsberg SC. et al. Synovial fluid interleukin 6, tumor necrosis factor, and nitric oxide values in dogs with osteoarthritis secondary to cranial cruciate ligament rupture. Am JVet Res 1997; 58: 1027-32.
14 Hewicker-Trautwein M, Carter SD, Bennett D. et al. Immunocytochemical demonstration of lymphocyte subsets and MHC class II antigen expression in synovial membranes from dogs with rheumatoid arthritis and degenerative joint disease. Vet Immunol Immunopathol 1999; 67: 341-57.
15 Kohn B, Garner M, Lübke S. et al. Polyarthritis following vaccination in four dogs. Vet Comp Orthop Traumatol 2003; 16: 6-10.
16 Kohn B. Canine immune-mediated polyarthritis. In: Proceedings. WSAVA, Bangkok, 2003; 440-3.
17 May C, Hughes DE, Carter SD. et al. Lymphocyte populations in the synovial membranes of dogs with rheumatoid arthritis. Vet Immunol Immunopathol 1992; 31: 289-300.
18 Nash MA, Lenzi R, Platsoucas CD. et al. RT-PCR quantitation of cytokine responses in vivo from specimens containing small numbers of cells during bioimmunotherapy. J Immunol Methods 1998; 219: 169-79.
19 Rottman JB, Tompkins WA, Tompkins MB. A reverse transcription-quantitative competitive polymerase chain reaction (RT-qcPCR) technique to measure cytokine gene expression in domestic mammals. Vet Pathol 1996; 33: 242-8.
20 Schumacher HR, Newton C, Halliwell RE. Synovial pathologic changes in spontaneous canine rheumatoid-like arthritis. Arthritis Rheum 1980; 23: 412-23.
21 St Clair EW. Interleukin-10: therapeutic prospects in rheumatoid arthritis. Curr Dir Autoimmun 2000; 2: 126-49.
22 Van den Berg WB. Arguments for interleukin 1 as a target in chronic arthritis. Ann Rheum Dis 2000; 59 (S1) 81-4.
23 Van den Berg WB. Anti-cytokine therapy in chronic destructive arthritis. Arthritis Res 2001; 3 (1) 18-26.
24 Venn G, Nietfeld JJ, Duits AJ. et al. Elevated synovial fluid levels of interleukin-6 and tumor necrosis factor associated with early experimental canine osteoarthritis. Arthritis Rheum 1993; 36 (6) 819-26.
25 Vervoordeldonk MJ, Tak PP. Cytokines in rheumatoid arthritis. Curr Rheumatol Rep 2002; 4 (3) 208-17.
26 Yuan GH, Masuko-Hongo K, Kato T. et al. Immunologic intervention in the pathogenesis of osteoarthritis. Arthritis Rheum 2003; 48 (3) 602-11.