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

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-IRA, 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-IRA 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.