In Vivo Blockade of Macrophage Migration Inhibitory Factor Ameliorates Acute Experimental Autoimmune Encephalomyelitis by Impairing the Homing of Encephalitogenic T Cells to the Central Nervous System

Abstract

Macrophage migration inhibitory factor (MIF) is a cytokine that plays a critical role in the regulation of macrophage effector functions and T cell activation. However, its role in the pathogenesis of T cell-mediated autoimmune diseases, such as experimental autoimmune encephalomyelitis (EAE), has remained unresolved. In this study, we report that anti-MIF Ab treatment of SJL mice with acute EAE improved the disease severity and accelerated the recovery. Furthermore, the anti-MIF treatment impaired the homing of neuroantigen-reactive pathogenic T cells to the CNS in a VCAM-1-dependent fashion. Interestingly, MIF blockade also decreased the clonal size of the neuroantigen-specific Th1 cells and increased their activation threshold. Taken together, the results demonstrate an important role for MIF in the pathogenesis of EAE/multiple sclerosis and suggest that MIF blockade may be a promising new strategy for the treatment of multiple sclerosis.

Macrophage migration inhibitory factor (MIF) gene polymorphism is associated with susceptibility to but not severity of inflammatory polyarthritis

“…Several investigators have suggested the use of anti-MIF therapy. [16][17][18] Our data support such a use in the potential treatment of patients with IP.…”

Xenopus laevis Macrophage Migration Inhibitory Factor Is Essential for Axis Formation and Neural Development

“…The significance of MIF in the immune system is being recognized to an increasing extent. Clinically, MIF is emerging as a prospective target of therapy for human diseases primarily affecting immunity (35,(37)(38)(39)(40). On the other hand, a number of findings have revealed many functions of MIF that are not restricted to those carried out as part of the immune system (9 -12, 39, 41-44).…”

Macrophage migration inhibitory factor is essential for allergic asthma but not for Th2 differentiation

“…Controls were exposed to aerosol of PBS. In the antibody-based interventions, OVA-sensitized BALB/c mice received a daily dose of 12.5 lg/g of anti-MIF mAb (XIV.15.5) [21] or isotype control via i.p. route starting the day before the aerosol challenge.…”

“…Th1 conditions: IFN-c (100 ng/mL; PeproTech), IL-12 (10 ng/mL; PeproTech) and anti-IL-4 (20 lg/mL; 11B11); Th2 conditions: IL-4 (50 ng/mL; PeproTech) and anti-IFN-c (XMG1.2; 100 lg/ mL). The concentrations of recombinant MIF and anti-MIF (XIV.15.5) [21] were 100 ng/mL and 100 lg/mL, respectively. After 24 h of primary stimulation, IL-2 (20 U/mL) was added to the cultures.…”

“…Once released, MIF can counterregulate the anti-inflammatory effects of steroids on cytokine production [15]. By means of antibody neutralization or gene deletion it has been demonstrated that MIF plays an important role in the pathogenesis of several inflammatory disorders, such as sepsis, glomerulonephritis, arthritis, colitis, encephalomyelitis, leishmaniasis and atherosclerosis [11,12,[16][17][18][19][20][21][22][23]. Increased MIF expression has also been observed in patients suffering from inflammatory diseases including sepsis, rheumatoid arthritis, acute respiratory distress syndrome (ARDS) and asthma [11,12,18,[24][25][26][27][28][29].…”