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 ty pe II collagen (RCII) administered in Freund's incomplete adjuvant oil (FIA) or with only FIA. If ovalbumin (Ova), is added to these arthrit ogens the development of arthritis is blocked. To investigate the mech anisms responsible for induction of arthritis, as well as inhibition o f 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 RC II/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 expre ssion of IFN-gamma mRNA was limited in RCII/FIA- and FIA-immunized rat s, whereas IL-2 mRNA expression was detected only after RCII/FIA injec tion. Lymph node cells from RCII-immunized animals generated a high am ount of TNF-alpha mRNA after restimulation with RCII, whereas restimul ation with the mitogen Con A generated a cytokine mRNA response domina ted by IL-2 and IFN-gamma. These and other results indicate that a str ong local expression of TNF-alpha, induced by arthritogenic stimuli, m ay be important for the induction of arthritis. Moreover, the elicitat ion of an immune reaction against Ova, may inhibit arthritis developme nt by contributing to a shift in the initial arthritogenic cytokine re sponse.