TNF-ALPHA DOMINATES CYTOKINE MESSENGER-RNA EXPRESSION IN LYMPHOID-TISSUES OF RATS DEVELOPING COLLAGEN-INDUCED AND OIL-INDUCED ARTHRITIS

Experimental arthritis can be induced in the DA rat strain with rat type II collagen (RCII) administered in Freund's incomplete adjuvant oil (FIA) or with only FIA. If ovalbumin (Ova), is added to these arthritogens the development of arthritis is blocked. To investigate the mechanisms responsible for induction of arthritis, as well as inhibition of arthritis, a kinetic study of the local cytokine expression in lymph nodes has been performed after immunization with the above mentioned agents. By using in situ hybridization techniques, mRNA expression of TNF-alpha, IL-2, IFN-gamma and IL-4 was determined. The results show a rapid and pronounced accumulation of TNF-alpha mRNA expression, in RCII/FIA and FIA immunized rats. This pronounced expression of TNF-alpha mRNA was not recorded in the Ova/FIA immunized animals, which instead were the only animals in which the IL-4 gene was expressed. The expression of IFN-gamma mRNA was limited in RCII/FIA- and FIA-immunized rats, whereas IL-2 mRNA expression was detected only after RCII/FIA injection. Lymph node cells from RCII-immunized animals generated a high amount of TNF-alpha mRNA after restimulation with RCII, whereas restimulation with the mitogen Con A generated a cytokine mRNA response dominated by IL-2 and IFN-gamma. These and other results indicate that a strong local expression of TNF-alpha, induced by arthritogenic stimuli, may be important for the induction of arthritis. Moreover, the elicitation of an immune reaction against Ova, may inhibit arthritis development by contributing to a shift in the initial arthritogenic cytokine response.