Macrophage migration inhibitory factor (MIF) is a regulator of inflammation that also has roles in cancer and autoimmune diseases. MIF exhibits both tautomerase and oxidoreductase activities, although how these are linked to MIF’s physiological and pathophysiological actions is unclear. MIF antagonist, also known as ISO-1, is an inhibitor of the dopachrome tautomerase activity of MIF in vitro (IC50 = 7 μM) and in cells (IC50 = 25 μM). It blocks the activation of NF-κB and TNF-α secretion from LPS-treated macrophages and improves the survival of mice following sepsis. MIF antagonist also demonstrates protective effects in airway and gastrointestinal inflammation in mice.