MIF
Macrophage migration inhibiting factor (MIF) is a critical mediator of innate, cell-mediated immunity, immunoregulation, and inflammation. MIF plays a key role in the regulation of macrophage function in host defense through the suppression of anti-inflammatory effects of glucocorticoids. MIF is elevated in several human inflammatory disorders (RA, MS, atherosclerosis, airways inflammation), and in the bloodstream of patients with severe sepsis. In general, the levels of MIF associate with disease severity. Exogenous MIF is pro-inflammatory and exacerbates disease. Neutralization of MIF by antiserum or elimination of MIF via genetic manipulation results in inhibition of the inflammatory response and diminishes disease progression in multiple animal models of disease. Anti-MIF antibodies also suppress tumor growth and effectively reduce tumor-associated angiogenesis. MIF precedes TNF-alpha in the inflammation cascade, and down-regulation of MIF directly reduces levels of TNF-alpha and other pro-inflammatory factors.
Carolus’ scientific founders have identified the chemokine receptors CXCR2 and CXCR4 as functional receptors for MIF1. MIF triggers directed migration, recruitment and arrest of leukocytes through functional interactions with CXCR2 and CXCR4. By activating both CXCR2 and CXCR4, MIF acts as a major regulator of inflammatory cell recruitment and atherogenesis. Blockade of MIF induces plaque regression and reduces monocyte and T-cell content in plaque of animals with advanced atherosclerosis.
1Bernhagen et al., Nature Medicine, 2007;
[PubMed Reference]