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Synovial Tissue Response to Treatment: The Effects of IFN-β Treatment in Rheumatoid Arthritis Patients

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Analysis of serial synovial biopsy specimens may provide useful surrogate end points for clinical studies. This approach could lead to a rapid screening method requiring relatively low numbers of patients for predicting the effects of novel anti-rheumatic drugs [1]. Before the therapeutic effects on synovial tissue (ST) could be properly analyzed, studies were conducted to establish the methods for synovial biopsy [2], microscopic examination [3], the relationship between the immunohistologic characteristics and disease activity [4], and the features of serial biopsies after placebo treatment [5].

This approach was used to evaluate the effects of IFN-β therapy on ST from RA patients [6]. Eleven patients were treated for 12 weeks with purified natural fibroblast IFN-β (Frone®, Ares-Serono) s.c. 3 times weekly with the following dosages: 6 million units (MIU) (n = 4), 12 MIU (n = 3), and 18 MIU (n = 4). Synovial biopsy specimens were obtained by needle arthroscopy at 3 time points: directly before and at 1 month and 3 months after initiation of treatment. Immunohistologic analysis was performed to detect CD3, CD38, CD68, CD55, TNF-α, IL-1β, IL-6, MMP-1, and TIMP-1. A significant reduction in the mean immunohistologic scores for CD3+ T cells, CD38+ plasma cells, and expression of IL-1β, IL-6, MMP-1, and TIMP-1 was observed in ST after treatment. The scores for CD68+ macrophages and TNF-α expression also tended to decrease, but these differences did not reach statistical significance. The inhibitory effects of IFN-β on MMP-1 production by fibroblast-like synoviocytes were confirmed by in vitro studies.

The significant changes in synovial tissue after IFN-β treatment support the view that IFN-β therapy has immunomodulating effects on rheumatoid synovium and might help to diminish both joint inflammation and destruction.

References

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    Tak PP, Breedveld FC: Analysis of serial biopsies as a screening method for predicting the effects of therapeutic interventions. J Clin Rheumatol. 1997, 3: 186-187.

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    Youssef PP, Kraan M, Breedveld F, et al: Quantitative microscopic analysis of inflammation in rheumatoid arthritis synovial membrane samples selected at arthroscopy compared with samples obtained blindly by needle biopsy. Arthritis Rheum. 1998, 41: 663-669. 10.1002/1529-0131(199804)41:4<663::AID-ART13>3.3.CO;2-C.

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    Kraan MC, Haringman JJ, Ahern MJ, Breedveld FC, Smith MD, Tak PP: Digital image analysis for the quantification of the cell infiltrate in synovial tissue. Rheumatology.

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    Tak PP, Smeets TJM, Daha MR, et al: Analysis of the synovial cellular infiltrate in early rheumatoid synovial tissue in relation to local disease activity. Arthritis Rheum. 1997, 40: 217-225.

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    Smeets TJM, Kraan MC, Versendaal H, Breedveld FC, Tak PP: Analysis of serial biopsies in rheumatoid arthritis patients: description of a control group without clinical improvement after treatment with recombinant human interleukin-10 or placebo. J Rheumatol.

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    Smeets TJM, Dayer JM, Kraan MC, et al: The effects of interferon-β treatment on synovial inflammation and metalloproteinase production in patients with rheumatoid arthritis. Arthritis Rheum.

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Keywords

  • Rheumatoid Arthritis Patient
  • Synovial Tissue
  • Synovial Biopsy
  • Rheumatoid Synovium
  • Immunohistologic Analysis