Cytokine gene activation in synovial membrane, regional lymph nodes, and spleen during the course of rat adjuvant arthritis

Cytokine gene activation was assessed during rat adjuvant arthritis (AA) in synovial membrane (SM), popliteal lymph node (popl-LN), and spleen, using semiquantitative, competitive RT-PCR. Changes in the popl-LN were considera bly higher than in spleen or SM. In the preclinical phase (day 6), cytokine mRNA elevations occurred exclusively in the popl-LN and included IFN-gamma , IL-1 beta, IL-5, IL-6, and IL-10. In the acute phase (days 13-16) all thr ee organs became involved: (i) in the SM, significant elevations were limit ed to IL-1 beta and IL-6, which, notably, correlated positively with the de gree of arthritis; (ii) in the popl-LN, IFN-gamma, IL-1 beta, IL-6, and IL- 10 (but not IL-5) were still elevated, while IL-2 rose significantly; (iii) in the spleen, TNF-alpha peaked simultaneously with the arthritis score (d ay 16) and dramatically dropped thereafter. Upon transition into the chroni c phase (day 20) the following phenomena were observed: (i) IL-1 beta and I L-6 were still significantly increased in the SM; (ii) IFN-gamma, IL-1 beta , IL-2, IL-6, and IL-10 were still elevated in the popl-LN; and (iii) there was a progressive rise of IL-5 mRNA in the spleen, positively correlated w ith the arthritis score. In conclusion, cytokines with pro- and anti-inflam matory functions overlap throughout disease, but in different organ-related patterns. Local (SM) and regional (popl-LN) IL-1 beta and IL-6, elevated t hroughout the entire course of AA, may directly contribute to disease sever ity. While in AA, spleen TNF-alpha appears to be a systemic marker of acute disease, spleen IL-5 may be involved in disease resolution. (C) 1999 Acade mic Press.