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Ann Rheum Dis. Oct 2000; 59(10): 781–787.
PMCID: PMC1753002

Effect of thrombin inhibition on synovial inflammation in antigen induced arthritis


OBJECTIVE—To determine the effect of the thrombin inhibitor, hirudin, on the pathogenesis of murine antigen induced arthritis (AIA).
METHODS—AIA was induced by intra-articular injection of methylated bovine serum albumin in the knee joints of previously immunised mice. Hirudin (injected subcutaneously 3 × 200 µg/mouse/day) was given over 13 days, starting three days before arthritis onset, and its anticoagulant effect monitored by clotting times. Arthritis severity was evaluated by technetium-99m (99mTc) uptake in the knee joints and by histological scoring. In addition, intra-articular fibrin deposition was examined by immunohistochemistry, and synovial cytokine mRNA expression measured by RNase protection.
RESULTS—Joint inflammation, measured by 99mTc uptake, was significantly reduced in hirudin treated mice at days 7 and 10 after arthritis onset. Histologically, synovial thickness was markedly decreased in hirudin treated mice compared with untreated ones. By contrast, no difference in articular cartilage proteoglycan content was found between both groups. Intra-articular fibrin deposition and synovial interleukin 1β mRNA levels, were slightly reduced (~20%) in arthritic joints from hirudin treated mice compared with untreated ones at day 10 of AIA.
CONCLUSION—Hirudin reduces joint inflammation associated with AIA by fibrin-dependent and independent mechanisms.

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Selected References

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Figures and Tables

Figure 1
Anti-methylated bovine serum albumin (anti-mBSA) antibody levels in control and hirudin treated mice with antigen induced arthritis (AIA). The results were expressed as a percentage of the anti-mBSA antibody content in the plasma of untreated arthritic ...
Figure 2
Time course of knee joint inflammation in hirudin treated mice with antigen induced arthritis. Joint inflammation was measured by external gamma counting of 99mTc uptake on days 3, 7, and 10 after antigen challenge into the right ...
Figure 3
Histologies and immunohistologies of whole knee joint sections of control and of hirudin treated mice with antigen induced arthritis. Figures A and C show safranin O stained sections of arthritic knee joints at day 10 after arthritis induction. ...
Figure 4
Histological grading and fibrin scoring of arthritic knee joints. Synovial thickness (A) and cartilage damage (B) were scored histologically using an arbitrary scale from 0 to 3. Fibrin deposition (C) was scored in the synovial membrane ...
Figure 5
Synovial cytokine mRNA levels in knee joints from untreated or hirudin treated mice. Total RNA was prepared from non-arthritic (left knee) or from arthritic (right knee) joints of untreated or hirudin treated mice at day 10 after induction of ...

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