Dynamics of proinflammatory cytokine expression in the joints of mice with collagen-induced arthritis (CIA)

Abstract

This report contains a description of the cellular localization and kinetics of proinflammatory cytokine expression in murine CIA, a model for rheumatoid arthritis. Tissue cryostat sections of undecalcified paws from type II collagen‐immunized DBA/1 mice, taken 1–10 days after the onset of clinical arthritis, were examined for the presence of tumour necrosis factor‐alpha (TNF‐α), IL‐1β and IL‐6 using an indirect immunoperoxidase technique. In parallel, interferon‐gamma (IFN‐γ) production by lymph node cells, stimulated in vitro with type II collagen, was assessed as a marker of T cell activity. The main areas of TNF‐α, IL‐1β 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. There was a progressive increase in the number of TNF‐α‐, IL‐1β‐ and IL‐6‐positive cells from day 1 to day 10 of arthritis, during which time IFN‐γ production by CD4⁺ T cells from draining lymph nodes declined sharply. A further finding of potential significance was that TNF‐α was consistently detected at day 1 of arthritis, whereas IL‐1β‐positive cells were not found until day 3, suggesting that the expression of TNF‐α precedes that of IL‐1β.