J Korean Rheum Assoc.  2007 Sep;14(3):201-207. 10.4078/jkra.2007.14.3.201.

The Suppressive Effect of Rifampicin in Animal Model of Hemophilic Synovitis

• Lee SH
• Lee YA
• Park EK
• Kim KS
• Cho YJ
• Han JS
• Yoo MC
• Yang HI

• KMID: 2202168
• DOI: http://doi.org/10.4078/jkra.2007.14.3.201

Abstract

OBJECTIVE
Hemophilic arthropathy, which results from recurrent intra-articular bleeding, is a proliferative synovitis, but the sequence of pathogenic events in hemophilic synovitis (HS) is not known in detail. To investigate the pathogenic mechanism of HS and to evaluate the suppressive effect of rifampicin for HS, we designed this study.
METHODS
Twenty normal male New Zealand white rabbits weighing approximately 2,000 gm were used for this study. We injected 1 mL of autologous whole blood of the rabbits into the right knee joint and normal saline into the left knee joint (control) thrice a week for 10 weeks and sacrificed 10 of them. We injected 10 mg of rifampicin into the right knee joint of HS, which is 5 rabbits of remained 10, once a week from 11th week until 15th week. At 11th week and 20th week, the rabbits were sacrificed and both knee joints of each rabbit were opened, synovial membrane specimens were collected and examined pathologically and biologically such as mRNA of IL-1, TNF-alpha, MMP-1 and MMP-3 in hemophilic synovium using by real-time quantitative PCR method (comparative Ct method).
RESULTS
At 20th week, in rifampicin treated group showed decreased proliferative, and infiltrated mononuclear cells compared with control group. And mRNA of TNF-alpha, IL-1 and MMP-3 levels were decreased also.
CONCLUSION
In animal model of HS, histological changes showed the same as human hemophilic synovitis. And this study suggested that rifampicin has a controlling effect on the inflammatory process of HS by suppression of inflammatory cytokine production in the experimental hemophilic synovitis model.

Keyword

Hemophilia; Synovitis; Rifampicin; Cytokine

MeSH Terms

Animals*
Hemophilia A
Hemorrhage
Humans
Interleukin-1
Knee Joint
Male
Models, Animal*
Polymerase Chain Reaction
Rabbits
Rifampin*
RNA, Messenger
Synovial Membrane
Synovitis*
Tumor Necrosis Factor-alpha
Interleukin-1
RNA, Messenger
Rifampin
Tumor Necrosis Factor-alpha

Figure

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  Fig. 1. The blood injected knee of rabbit (arrow) was more swollen compared with the other knee.

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  Fig. 2. The blood injected right knee shows degenerative change by X-ray.

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  Fig. 3. The synovium of blood injected knee shows proliferation and fat tissue was increased under synovium (A) normal saline injected knee synovium (B) blood injected knee synovium (H&E stain, x 400).

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  Fig. 4. The expression of TNF-α, IL-1, MMP-1 and MMP-3 mRNA in synovium of animal model of Hemathrosis (HA) by real time-PCR. Control is saline-injected knee, HA is blood-injected synovium without rifampicin, and RFP is blood-injected synovium treated with rifampicin.

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