How glucocorticoids control their own strength and the balance between pro- and anti-inflammatory mediators.

The very powerful anti-inflammatory properties of glucocorticoids (GC) have enabled researchers to use them to treat a variety of inflammatory and autoimmune diseases. The potential of GC lies in their ability to inhibit the production of pro-inflammatory cytokines and mediators by gene repression as well as by gene induction. Paradoxically, GC seem to control their own strength by inducing the pro-inflammatory cytokine macrophage migration inhibitory factor (MIF), which negatively regulates the anti-inflammatory capacities of GC. The mechanism by which MIF inhibits the actions of GC is addressed by Roger et al. in this issue of the European Journal of Immunology. They report that MIF inhibits GC-induction of the mitogen activated protein kinase (MAPK) phosphatase-1 (MKP-1), a phosphatase that inhibits the activation of pro-inflammatory MAPK. We comment here on their findings and place their work in the broader context of the physiological role of MIF and the potential therapeutic targeting of glucocorticoid resistance.