Local steroid activation is a critical mediator of the anti-inflammatory actions of therapeutic glucocorticoids.

We identify an entirely novel component of therapeutic GC action, whereby following their systemic metabolism, they require peripheral reactivation and amplification by 11β-HSD1 at sites of inflammation to deliver their anti-inflammatory therapeutic effects. This study provides a novel mechanistic understanding of the anti-inflammatory properties of therapeutic GCs and their targeting to sites of inflammation in polyarthritis.