Temporal expression of cytokines and chemokines in rat adjuvant-induced arthritis

Adjuvant-induced arthritis (AIA) in rats is a relevant model for human rheumatoid arthritis (RA). In this study, th expression of the cytokines TNF-alpha, IL-1 and IL-6, as well as the chemokines MIP-1-alpha, MCP-1 and ENA-78 in the sera and joint homogenates of AIA and control, sham-injected rats was studied over a 47-day period. All of these cytokines and chemokines showed increased production in AIA. In addition, TNF-alpha, IL-1, ENA-78 and MIP-1-alpha could be termed as "early" mediators, as their production increased in the first 14-21 days and it correlated with early events in synovitis, such as neutrophil ingress, joint swelling and general symptoms. TNF-alpha may have mostly systemic, while IL-1 mainly local synovial effects. IL-6 and MCP-1 were found to be "late" inflammatory mediators, as their secretion was up-regulated after 2 weeks post-adjuvant injection and remained high during the observation period. Also, significant correlation was found between the production of TNF-alpha and that of chemokines. In conclusion, the differential expression of "early" and "late" cytokines and chemokines may account for various events underlying synovitis in AIA.