Macrophage Migration Inhibitory Factor in Protozoan Infections

Abstract

<jats:p>Macrophage migration inhibitory factor (MIF) is a cytokine that plays a central role in immune and inflammatory responses. In the present paper, we discussed the participation of MIF in the immune response to protozoan parasite infections. As a general trend, MIF participates in the control of parasite burden at the expense of promoting tissue damage due to increased inflammation.</jats:p>

Novel Anti-inflammatory Activity of Epoxyazadiradione against Macrophage Migration Inhibitory Factor

“…The tautomerase activity of MIFs was also regained by diluting the inactivated MIFs 10-fold, which further proved its reversible nature of inhibition. This non-competitive reversible binding of epoxyazadiradione with MIFs makes it a favorable candidate molecule against the MIF-induced proinflammatory diseases because the other well known MIF inhibitor, ISO-1, is a covalent inhibitor and inhibits huMIF but fails to inhibit MIF activity of parasitic origin (5,19,29). In contrast, epoxyazadiradione inhibits tautomerase activity of MIF of both plasmodial and human origin.…”

“…Higher levels of MIF have been found both systemically and within affected tissues in patients with multiple sclerosis, sepsis, diabetes mellitus, glomerulonephritis, psoriasis, rheumatoid arthritis, systemic lupus erythematosus, atherosclerosis, inflammatory bowel disease, Guillain-Barré syndrome, neuro-Behçet disease, malarial anemia, gastric ulcer, Parkinson disease, hepatocellular carcinoma, breast cancer, and bladder urothelial cell carcinoma (9 -17). MIF also has a role in deter-mining the outcome of infections caused by different parasites, bacteria, and viruses such as helminths (18), Leishmania (19), nematodes (20), malaria (21), Streptococcus (22), and dengue virus (23). Block of endogenous MIF by a small molecule such as (S,R)-3-(4-hydroxyphenyl)-4,5-dihydro-5-isoxazole acetic acid methyl ester (ISO-1) or sulforaphane and neutralization of MIF by anti-MIF antibodies or by plant-derived MIF inhibitors reduces the manifestations of immune inflammatory disorders in numerous preclinical models such as type II collagen-induced arthritis, immunologically induced kidney disease, experimental autoimmune encephalomyelitis, experimental allergic neuritis, immunoinflammatory diabetes, experimental autoimmune myocarditis, irradiation-induced acute pneumonitis, sepsis, and ischemia-reperfusion injury (14, 24 -27).…”

“…The well known inhibitor ISO-1 is very specific to the human MIF (huMIF) and unable to inhibit MIF of hookworm (29), Leishmania (19), and P. yoelii (5). Inflammatory diseases are currently treated with steroidal and non-steroidal anti-inflammatory drugs (30).…”

Macrophage migration inhibitory factor, a role in COPD

“…Its function is mostly proinflammatory with chemokinelike properties (4) via binding and activation of CD74 receptors found in a variety of tissues, initiating cytokine release and cell proliferation (23). MIF has a significant role in the innate immune defense against acute viral and bacterial infection (20,30), tuberculosis (12), and protozoan diseases (6). On the other hand, MIF may also contribute to the exaggerated inflammation observed with sepsis and ARDS (10,22).…”

Implications of SNPs on toll-like receptor genes in malaria: what do we know?

“…The immune system has been shaped by the process of evolution into an efficient system that allows the coexistence of pathogenic agents in hosts while controlling infections 3 . Knockout murine models of genes involved in the innate immune response have shown the key role played by TLRs in Plasmodium spp.…”