Deficiency of the macrophage migration inhibitory factor gene has no significant effect on endotoxaemia.
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.
Honma
N
N
Pharmaceutical Research Laboratory, Kirin Brewery Co. Ltd, Gunma, Japan.
Koseki
H
H
Akasaka
T
T
Nakayama
T
T
Taniguchi
M
M
Serizawa
I
I
Akahori
H
H
Osawa
M
M
Mikayama
T
T
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
D000893:Anti-Inflammatory Agents; D008070:Lipopolysaccharides; D008263:Macrophage Migration-Inhibitory Factors; D014409:Tumor Necrosis Factor-alpha; D003907:Dexamethasone