DYNAMICS OF PROINFLAMMATORY CYTOKINE EXPRESSION IN THE JOINTS OF MICEWITH COLLAGEN-INDUCED ARTHRITIS (CIA)

This report contains a description of the cellular localization and ki netics of proinflammatory cytokine expression in murine CIA, a model f or rheumatoid arthritis. Tissue cryostat sections of undecalcified paw s from type II collagen-immunized DBA/1 mice, taken 1-10 days after th e onset of clinical arthritis, were examined for the presence of tumou r necrosis factor-alpha (TNF-alpha), IL-1 beta and IL-6 using an indir ect immunoperoxidase technique. In parallel, interferon-gamma (IFN-gam ma) production by lymph node cells, stimulated in vitro with type 11 c ollagen, was assessed as a marker of T cell activity. The main areas o f TNF-alpha, IL-1 beta and IL-6 expression were in the synovial lining layer and in tissue contiguous with cartilage and bone (the marginal zone), in particular at sites of pannus formation and joint erosion. T here was a progressive increase in the number of TNF-alpha-, IL-1 beta - and IL-6-positive cells from day 1 to day 10 of arthritis, during wh ich time IFN-gamma production by CD4(+) T cells from draining lymph no des declined sharply. A further finding of potential significance was that TNF-ol was consistently detected at day 1 of arthritis, whereas I L-1 beta-positive cells were not found until day 3, suggesting that th e expression of TNF-alpha precedes that of IL-1 beta.