Cytokine mRNA in the joints and draining lymph nodes of rats with adjuvant arthritis and effects of cyclosporin A

Inflammation. 2000 Oct;24(5):447-61. doi: 10.1023/a:1007064212462.


TNF-alpha and IL-1beta 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-alpha, IL-1beta, IL-6, IFN-gamma, 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-alpha and IFN-gamma mRNA were increased in the PLN before clinical signs of arthritis. This was followed by increases in IL-1beta and IL-1RA mRNA at d9 and IL-6 mRNA at d12. PLN IL-1RA mRNA levels were positively correlated with those of IL-1beta and TNF-alpha throughout d5-d20. IL-4 mRNA levels were highest on days 7 and 20. In the synovium, a small increase in TNF-alpha, IL-1beta, and IL-6 mRNA was detected on d5 then again on d12. Maximal synovial TNF-alpha levels were reached on d20, while IL-1beta peak expression was on d16 and IL-6 on d14. IL-4, IL-1RA, and IFN-gamma 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-1beta or TNF-alpha was lost in treated animals. Thus there is a variable pattern of cytokine gene expression in rat AA, the undetectable IL-4 and IFN-gamma mRNA in synovium being analogous to human rheumatoid arthritis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arthritis, Experimental / drug therapy
  • Arthritis, Experimental / genetics
  • Arthritis, Experimental / metabolism*
  • Arthritis, Rheumatoid / metabolism
  • Chemotaxis, Leukocyte / drug effects
  • Cyclosporine / pharmacology*
  • Cyclosporine / therapeutic use
  • Cytokines / biosynthesis
  • Cytokines / genetics*
  • Disease Models, Animal
  • Gene Expression Regulation / drug effects*
  • Humans
  • Hypersensitivity, Delayed / immunology
  • Immunosuppressive Agents / pharmacology*
  • Immunosuppressive Agents / therapeutic use
  • Interferon-gamma / biosynthesis
  • Interferon-gamma / genetics
  • Interleukin 1 Receptor Antagonist Protein
  • Interleukin-1 / biosynthesis
  • Interleukin-1 / genetics
  • Interleukin-4 / biosynthesis
  • Interleukin-4 / genetics
  • Interleukin-6 / biosynthesis
  • Interleukin-6 / genetics
  • Lymph Nodes / metabolism*
  • Male
  • Models, Animal
  • RNA, Messenger / biosynthesis*
  • Rats
  • Rats, Inbred Lew
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sialoglycoproteins / biosynthesis
  • Sialoglycoproteins / genetics
  • Synovial Membrane / metabolism*
  • Tarsus, Animal / metabolism
  • Tumor Necrosis Factor-alpha / biosynthesis
  • Tumor Necrosis Factor-alpha / genetics


  • Cytokines
  • IL1RN protein, human
  • Immunosuppressive Agents
  • Interleukin 1 Receptor Antagonist Protein
  • Interleukin-1
  • Interleukin-6
  • RNA, Messenger
  • Sialoglycoproteins
  • Tumor Necrosis Factor-alpha
  • Interleukin-4
  • Interferon-gamma
  • Cyclosporine