The effects of interferon-β (IFN-β) treatment on synovial cytokine expression in collagen induced arthritis in DBA/1 mice

Objective

IFN-β is believed to have immunomodulatory properties which might have a beneficial effect in rheumatoid arthritis (RA) by inhibition of TNF-α and enhancement of IL-10 and IL-1RA production, as has been shown in vitro. The aim of this study was to evaluate the effect of IFN-β treatment on cytokine expression in vivo in an animal model of RA.

Methods

DBA/1 male mice with collagen induced arthritis (CIA) were treated with daily intraperitoneal injections of IFN-β (2.5 mg/day, 1.25 mg/day, 0.25 mg/day), or NaCL for 7 days (n = 8–10). Treatment started on day 1, which represents the first day that clinical arthritis was detected in that mouse. The mice were sacrificed on day 8. Immunohistologic staining was performed on decalcified wax-embedded paw sections with polyclonal antibodies specific for TNF-α, IL-1β, IL-6, IL-10, and IL-18. The sections were evaluated by semiquantative analysis on a 5-point scale (0–4).

Results

There was a statistically significant decrease in the mean scores for expression of TNF-α and IL-6 in animals treated with the highest dose of IFN-β (2.5 mg/day) compared with the NaCL control group (TNF-α: NaCL: 2.9 ± 0.3 vs. IFN-β 1.4 ± 0.2) (IL-6: NaCL: 2.3 ± 0.3 vs. IFN-β 0.9 ± 0.3) (TNF-α : P < 0.05, IL-6: P < 0.05). IL-18 and IL-1β expression tended to be lower in IFN-β treated animals, but this difference did not reach statistical significance. Interestingly, IL-10 production was increased in the IFN-β treated animals (NaCL: 0.5 ± 0.3 vs. IFN-β: 1.6 ± 0.5), although not statistically significant.

Conclusion

The reduced expression of TNF-α, IL-6, IL-1β, and IL-18 and the increased expression of IL-10 in mice with CIA treated with IFN-β extends previous in vitro observations. Because of its immunomodulatory effects, IFN-β is a potential therapy for RA.