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Cytokine mRNA in the Joints and Draining Lymph Nodes of Rats with Adjuvant Arthritis and Effects of Cyclosporin A

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Abstract

TNF-α and IL-1β promote leukocyte recruitment to arthritic joints and may contribute to cartilage degradation while regulatory cytokines such as IL-4 and IL-1RA may in part determine the course of arthritis. Here we report the pattern of TNF-α, IL-1β, IL-6, IFN-γ, IL-1RA, and IL-4 mRNA expression, detected by RT/PCR, in the talar joint and draining popliteal lymph node (PLN) of rats with adjuvant arthritis (AA). Levels of TNF-α and IFN-γ mRNA were increased in the PLN before clinical signs of arthritis. This was followed by increases in IL-1β and IL-1RA mRNA at d9 and IL-6 mRNA at d12. PLN IL-1RA mRNA levels were positively correlated with those of IL-1β and TNF-α throughout d5-d20. IL-4 mRNA levels were highest on days 7 and 20. In the synovium, a small increase in TNF-α, IL-1β, and IL-6 mRNA was detected on d5 then again on d12. Maximal synovial TNF-α levels were reached on d20, while IL-1β peak expression was on d16 and IL-6 on d14. IL-4, IL-1RA, and IFN-γ mRNA was undetectable in the synovium. Cyclosporin treatment for 4 days, initiated at the height of arthritis, rapidly decreased clinical disease, and decreased migration of neutrophils and T lymphocytes into the joints. Yet no significant effect of CyA was observed on inflammatory cytokine expression, although the correlation between PLN IL-1RA and IL-1β or TNF-α was lost in treated animals. Thus there is a variable pattern of cytokine gene expression in rat AA, the undetectable IL-4 and IFN-γ mRNA in synovium being analogous to human rheumatoid arthritis.

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Authors and Affiliations

  1. Department of Pediatrics, Dalhousie University, Halifax, N.S., Canada, B3J 3G9

    L. M. Ayer

  2. Department of Pediatrics, Department of Pathology, Department of Microbiology and Immunology, Dalhousie University, Halifax, N.S., Canada, B3J 3G9

    A. C. Issekutz

  3. Department of Microbiology and Immunology, Dalhousie University, Halifax, N.S., Canada, B3J 3G9

    C. C. M. Waterhouse

  4. Department of Pediatrics, Department of Microbiology and Immunology, Dalhousie University, Halifax, N.S., Canada, B3J 3G9

    A. W. Stadnyk

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Ayer, L.M., Issekutz, A.C., Waterhouse, C.C.M. et al. Cytokine mRNA in the Joints and Draining Lymph Nodes of Rats with Adjuvant Arthritis and Effects of Cyclosporin A. Inflammation 24, 447–461 (2000). https://doi.org/10.1023/A:1007064212462

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