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

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.