Abstract
A marked proliferation of synovial fibroblasts in joints leads to pannus formation
in rheumatoid arthritis (RA). Various kinds of cytokines are produced in the pannus. The
purpose of this study is to elucidate the effects of phosphodiesterase 4 (PDE4) inhibitors
in a new animal model for the evaluation of pannus formation and cytokine production
in the pannus. Mice sensitized with methylated bovine serum albumin (mBSA) were
challenged by subcutaneous implantation of a membrane filter soaked in mBSA solution
in the back of the mice. Drugs were orally administered for 10 days. The granuloma
formed around the filter was collected on day 11. It was chopped into pieces and
cultured in vitro for 24 hr. The cytokines were measured in the supernatants. The type
of cytokines produced in the granuloma was quite similar to those produced in pannus
in RA. Both PDE4 inhibitors, KF66490 and SB207499, suppressed the production
of IL-1