Treatment of Lewis rats with the GR inhibitor RU38486 results in higher susceptibility to streptococcal-induced arthritis, a model that mimics certain aspects of RA.229 Similarly, in Lewis rats with adjuvant-induced arthritis, global inhibition of 11β-HSD1 using carbenoxolone results in significant edema and upregulation of synovial inflammatory cytokines including TNF-α without changing plasma corticosterone levels.227 Together, these two studies suggest endogenous GC signaling may have local anti-inflammatory effects in RA. Here, NR3C1 is linked to arthritic joint disease.