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

Objective. To examine cytokine and chemokine production during the evolutio n of rat adjuvant-induced arthritis (AIA), a model of rheumatoid arthritis. Methods. Clinical and laboratory assessment of the course of AIA was perfor med over a 47-day period. Levels of the cytokines tumor necrosis factor alp ha (TNF alpha), interleukin-1 beta (IL-1 beta), and IL-6, as well as levels of the chemokines macrophage inflammatory protein lar MIP-1 alpha and JE, the murine homolog of monocyte chemoattractant protein 1, were determined b y enzyme-linked immunosorbent assay in the sera and joints of AIA and contr ol rats. Synovia from AIA rats were (immuno)histochemically analyzed. Resul ts of cytokine and chemokine measurements were correlated with clinical and laboratory markers of inflammation and histology. Results. Early (before day 14 post adjuvant injection) and later phases of AIA could be distinguished. Cytokine and chemokine production nas increased in AIA versus control rats. The production of TNF alpha, IL-1 beta, MIP-1 alpha, and as determined earlier, epithelial neutrophil-activating peptide 78-like protein was abundant prior to and during the course of AIA, while t hat of IL-6 and JE was elevated in the late phase of AIA. Cytokine and chem okine levels were correlated with the clinical symptoms of arthritis and bl ood neutrophil counts. Joint levels of IL-1 beta showed correlation with sy novial lining proliferation and neutrophil ingress into AIA synovium. Conclusion. Cytokines and chemokines are involved ed in the clinical, labor atory, and histologic changes underlying AIA. The production of these media tors may be temporary and spatially regulated. These findings may be import ant for the optimal timing of cytokine and chemokine targeting.