Skip to main content
  • Meeting abstract
  • Published:

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

Full text

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

  1. 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.

    Article  PubMed  CAS  Google Scholar 

  2. 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.

    Article  PubMed  CAS  Google Scholar 

  3. 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.

  4. 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.

    Article  PubMed  CAS  Google Scholar 

  5. 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.

  6. 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.

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Tak, P.P. Synovial Tissue Response to Treatment: The Effects of IFN-β Treatment in Rheumatoid Arthritis Patients. Arthritis Res Ther 1 (Suppl 1), S39 (1999). https://doi.org/10.1186/ar53

Download citation

  • Published:

  • DOI: https://doi.org/10.1186/ar53

Keywords