Dynamics of proinflammatory cytokine expression in the joints of mice with collagen-induced arthritis (CIA).
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-alpha), IL-1beta and IL-6 using an indirect immunoperoxidase technique. In parallel, interferon-gamma (IFN-gamma) 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-alpha, IL-1beta 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-alpha-, IL-1beta- and IL-6-positive cells from day 1 to day 10 of arthritis, during which time IFN-gamma production by CD4+ T cells from draining lymph nodes declined sharply. A further finding of potential significance was that TNF-alpha was consistently detected at day 1 of arthritis, whereas IL- 1beta-positive cells were not found until day 3, suggesting that the expression of TNF-alpha precedes that of IL-1beta.
Marinova-Mutafchieva
L
L
Kennedy Institute of Rheumatology, London, UK.
Williams
R O
RO
Mason
L J
LJ
Mauri
C
C
Feldmann
M
M
Maini
R N
RN
D000818:Animals; D000843:Ankle Joint; D001169:Arthritis, Experimental / Q000378:metabolism*; D003094:Collagen; D006614:Hindlimb; D018836:Inflammation Mediators / Q000378:metabolism*; D007371:Interferon-gamma / Q000096:biosynthesis; D007375:Interleukin-1 / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis; D008198:Lymph Nodes / Q000378:metabolism; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D013583:Synovial Membrane / Q000378:metabolism; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D018836:Inflammation Mediators; D007375:Interleukin-1; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D003094:Collagen