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Paradox of Interferon Beta Therapy in Rheumatoid Arthritis

Strategic Insights

— 1 min read

Researchers from the University of California have been studying the effects of interferon beta (IFN beta) therapy on rheumatoid arthritis (RA). Despite its effectiveness in multiple sclerosis and murine models of arthritis, systematic IFN beta treatment induces only minimal improvement in RA. To understand this paradox, the researchers evaluated the mechanism of IFN beta benefit in passive K/BxN arthritis and the effect of IFN beta treatment on RA synovium.

Key Takeaways:

  • IFN beta therapy is effective in multiple sclerosis and murine models of arthritis, but only minimally effective in RA.
  • The anti-inflammatory effects of IFN beta in passive K/BxN arthritis are dependent on interleukin 1 receptor antagonist (IL-1Ra), but not interleukin 10 (IL-10).
  • Daily IFN beta treatment significantly decreased arthritis severity in IL-10-null mice, but not in IL-1Ra-null mice.
  • IFN beta treatment did not reduce histological scores in IL-1Ra-null mice or gene expression of articular cytokines and chemokines.
  • Paired synovial biopsy specimens from RA patients treated with IFN beta demonstrated a trend towards increased IL-1Ra and reduced IL-10 expression on day 85 levels compared with pretreatment specimens.
  • The researchers concluded that systemic IFN beta treatment in RA increases synovial IL-1Ra production, but also decreases IL-10 production.
  • The study highlights the complex mechanisms underlying IFN beta therapy in RA and suggests that the effects of IFN beta may depend on the specific cytokine profile.

Statistics:

  • 6 million IU, 12 million IU, or 18 million IU of purified natural fibroblast IFN beta (Frone) were used in the study.
  • IL-1Ra and IL-6 were measured by ELISA in the serum of treated mice.
  • A trend towards increased IL-1Ra and reduced IL-10 expression was observed in paired synovial biopsy specimens from RA patients treated with IFN beta.
  • The study found that systemic IFN beta treatment significantly decreased arthritis severity in IL-10-null mice, but not in IL-1Ra-null mice.

Sources:

  • M. Corr et al., "Interleukin 1 receptor antagonist mediates the beneficial effects of systemic interferon beta in mice: implications for rheumatoid arthritis," Annals of the Rheumatic Diseases, 2011; 70(5): 858-863.
  • University of California, Division of Rheumatol Allergy & Immunology, 9500 Gilman Dr., La Jolla, CA 92093, United States.
  • B M J Publishing Group, British Med Association House, Tavistock Square, London WC1H 9JR, England.

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