EXPRESSION OF CELL-ADHESION MOLECULES AND CYTOKINES IN MURINE ANTIGEN-INDUCED ARTHRITIS

Adhesion molecules and cytokines are important in chronic inflammatory conditions such as rheumatoid arthritis (RA) by virtue of their role in cell activation and emigration. Using immunohistochemical technique s we studied the expression of adhesion molecules and cytokines in cry opreserved sections of murine knee joint in the course of antigen-indu ced arthritis, an animal model of human RA. Various adhesion molecules and cytokines are expressed in the arthritic joint tissue. LFA-1, Mac -1, CD44, ICAM-1 and P-selectin were strongly expressed in the acute p hase and to a lesser degree in the chronic phase of arthritis. VLA-4 a nd VCAM-1 appeared to be moderately expressed on day 1, L-selectin bet ween days 1 and 3. LFA-1, Mac-1, CD44, alpha 4-integrin, ICAM-1 and th e selectins were found expressed on cells of the synovial infiltrate, LFA-1, Mac-1 and ICAM-1 on the synovial lining layer, and VCAM-1 and P -selectin on endothelial cells. Expression of E-selectin could be demo nstrated throughout the experiment at a low level in cells of the acut e cell infiltrate. Cytokines, especially IL-2, IL-4, IL-6, TNF, and IF N-gamma, were heavily expressed during the acute phase of arthritis in cellular infiltrate. Taken together these data demonstrate that cytok ines and their activation of adhesion molecules contribute to cell inf iltration and activation during the initial phase of arthritis and to the induction and progression of tissue destruction in arthritic joint s. These molecules might be potential targets for novel therapeutic st rategies in inflammatory and arthritic disorders.