MIF In Steroid Sparing

MIF has a unique relationship with glucocorticoids (also known as corticosteroids, or simply steroids). Glucocorticoids are naturally occurring anti-inflammatory hormones that temper the activity of the immune system and prevent its over-activation. This action of glucocorticoids has been exploited for over 50 years through the therapeutic use of glucocorticoid drugs.

Although effective in many contexts, glucocorticoid drugs are highly toxic due to dose-dependent metabolic effects. It is therefore a universal aim of physicians and patients to use lower doses of steroids. To date, there has been no mechanism-based way to reduce the dose of steroid required for a given effect (i.e. ‘steroid-sparing’) in humans.

MIF is induced by glucocorticoids, and acts to antagonize their effects. Therefore, inhibiting MIF should amplify the effect of glucocorticoids and result in a steroid-sparing effect. This has been recently proven, in studies by Cortical founders, which demonstrated a three-fold reduction in the requirement for steroid in the absence of MIF. This effect of MIF is based on its regulation of a key signal pathway regulatory molecule, MAP kinase phosphatase 1 (MKP1).

If translated to a clinical context, this would represent a major breakthrough. As glucocorticoids are used to treat virtually all inflammatory diseases, such a steroid-sparing therapy could have very wide application.

For more on the relationship between MIF and glucocorticoids, see Aeberli et al Rheumatology 2006 45(8):937-943