title: Deficiency of the macrophage migration inhibitory factor gene has no significant effect on endotoxaemia.
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.
authors.affiliation: Pharmaceutical Research Laboratory, Kirin Brewery Co. Ltd, Gunma, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Honma
authors.forename: H
authors.initials: H
authors.lastname: Koseki
authors.forename: T
authors.initials: T
authors.lastname: Akasaka
authors.forename: T
authors.initials: T
authors.lastname: Nakayama
authors.forename: M
authors.initials: M
authors.lastname: Taniguchi
authors.forename: I
authors.initials: I
authors.lastname: Serizawa
authors.forename: H
authors.initials: H
authors.lastname: Akahori
authors.forename: M
authors.initials: M
authors.lastname: Osawa
authors.forename: T
authors.initials: T
authors.lastname: Mikayama
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D019446:Endotoxemia / Q000276:immunology*; D005298:Fertility; D008070:Lipopolysaccharides / Q000276:immunology; D008262:Macrophage Activation / Q000187:drug effects / Q000276:immunology; D008263:Macrophage Migration-Inhibitory Factors / Q000172:deficiency* / Q000235:genetics / Q000276:immunology; D017737:Macrophages, Peritoneal / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D012772:Shock, Septic / Q000276:immunology; D015996:Survival Rate; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D000893:Anti-Inflammatory Agents; D008070:Lipopolysaccharides; D008263:Macrophage Migration-Inhibitory Factors; D014409:Tumor Necrosis Factor-alpha; D003907:Dexamethasone