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Deficiency of the macrophage migration inhibitory factor gene has no significant effect on endotoxaemia
1Pharmaceutical Research Laboratory, Kirin Brewery Co. Ltd, Gunma, Japan.
Abstract:
By targeted disruption of the MIF gene, we have established a mouse strain deficient in macrophage (Mphi) migration inhibitory factor (MIF). Despite previous reports indicating an essential role of MIF in endotoxaemia, an injection of lipopolysaccharide (LPS) into the MIF-deficient mice (maintained under specific pathogen-free conditions) caused shock. No significant difference was detected between the MIF-deficient mutant and normal mice in susceptibility to LPS for endotoxaemia or tumour necrosis factor-alpha (TNF-alpha) formation upon LPS injection. Peritoneal Mphi from the two strains produced TNF-alpha in response to LPS with similar dose responses. Dexamethasone suppressed the LPS-induced TNF-alpha response of Mphi, but no difference was detected between the Mphi from the two strains. These results suggest that endogenous MIF has no significant effect on the LPS-induced TNF-alpha production and no effect on suppression of the response by glucocorticoids. Thus, MIF is not crucial for LPS-induced immune responses leading to shock.
Insights
Macrophage migration inhibitory factor (MIF) deficiency did not alter endotoxaemia shock or tumor necrosis factor-alpha (TNF-alpha) production in mice following LPS injection. Endogenous MIF is not crucial for LPS-induced immune responses.
Area of Science:
- Immunology
- Molecular Biology
Background:
- Macrophage migration inhibitory factor (MIF) has been implicated in endotoxaemia.
- Its precise role in lipopolysaccharide (LPS)-induced immune responses requires further elucidation.
Purpose of the Study:
- To investigate the role of endogenous MIF in LPS-induced endotoxaemia and TNF-alpha production.
- To determine if MIF influences glucocorticoid suppression of immune responses.
Main Methods:
- Generation of a mouse strain with targeted disruption of the MIF gene.
- Administration of LPS to MIF-deficient and wild-type mice.
- Assessment of endotoxaemia, TNF-alpha production, and dexamethasone's effects on peritoneal macrophages.
Main Results:
- MIF-deficient mice exhibited similar susceptibility to LPS-induced endotoxaemia and shock as wild-type mice.
- LPS-induced TNF-alpha production by peritoneal macrophages was comparable between the two strains.
- Dexamethasone effectively suppressed LPS-induced TNF-alpha production in both MIF-deficient and wild-type macrophages, with no significant strain-specific differences.
Conclusions:
- Endogenous MIF does not play a significant role in LPS-induced TNF-alpha production or endotoxaemia.
- MIF is not essential for the immune response leading to LPS-induced shock.
- MIF does not influence the suppressive effects of glucocorticoids on LPS-induced TNF-alpha production.