| Autor: |
Guedez, Yajaira B., Whittington, Karen B., Clayton, Jenny L., Joosten, Leo A. B., Loo, Fons A. J. van de, Berg, Wim B. van den, Rosloniec, Edward F. |
| Zdroj: |
Arthritis & Rheumatism; October 2001, Vol. 44 Issue: 10 p2413-2424, 12p |
| Abstrakt: |
To determine whether the lack of interferon-γ (IFNγ) alters resistance to collagen-induced arthritis (CIA) in a nonsusceptible mouse strain, and if so, to identify changes in the antibody, cellular type II collagen (CII)specific immune responses, and cytokine gene expression that might account for the altered susceptibility. CIA-resistant C57BL/6 and C57BL/6 IFNγ−/− mice were immunized with bovine CII in Freund's complete adjuvant (CFA) or in CFA alone. Animals were monitored for signs of arthritis for up to 80 days; arthritis severity was assessed visually and histologically. Sera were collected at various time points after immunization for measurement of anti-CII antibody levels. T cell responses to bovine CII were assessed in proliferation assays. Cytokine messenger RNA (mRNA) expression in lymph node cells and in synovial cells from arthritic paws was measured by RNase protection assays, and levels of cytokine protein production were determined by enzyme-linked immunosorbent assay. IFNγ−/− mice developed a severe auto- immune arthritis that was dependent on immunization with CII. IFNγ−/− mice produced significantly higher amounts of IgG1 and IgG2b antibody to the autoantigen, murine CII, compared with wild-type C57BL/6 mice and had an enhanced T cell proliferative response to bovine CII. Enhanced production of mature interleukin-1/β (IL-1β) protein was observed, but no significant changes in Th1 or Th2 cytokines. Although IL-6 and tumor necrosis factor α transcripts were clearly evident in the synovial cells from the arthritic paws of IFNγ−/− mice, neither message was elevated to the levels measured for IL-1β expression. Treatment of IFNγ−/− mice with antiIL-1β significantly reduced the incidence and severity of the inflammation. Endogenous IFNγ plays a role in the regulation of IL-1β in this model of autoimmune arthritis. |
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