The effects of MIF on macrophage activation. Release of preformed MIF induced by different types of stimuli, such as infections, cytokines, and variations on glucocorticoid levels, has paracrine and exocrine effects: triggering of the CD44/CD74 receptor complex and the CXCR2 and CXCR4 chemokine receptors results in the production of tumor-necrosis-factor-α (TNF-α), interleukin-1 (IL-1), and nitric oxide (NO,) as well as of arachidonic acid and eicosanoids through the induction of phospholipase A₂ and cyclooxygenase, and in increased expression of TLRs and adhesion molecules in macrophages. The exocrine effects of MIF include induction of chemotaxis and promoting the survival of leukocytes.