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 (M phi) migration inhibitory factor (MIF). Despite previous reports indicating an essential role of MIF in endotoxaemia, an in jection of lipopolysaccharide (LPS) into the MIF-deficient mice (maintained under specific pathogen-free conditions) caused shock. No significant diff erence was detected between the MIF-deficient mutant and normal mice in sus ceptibility to LPS for endotoxaemia or tumour necrosis factor-alpha (TNF-al pha) formation upon LPS injection. Peritoneal M phi from the two strains pr oduced TNF-alpha in response to LPS with similar dose responses. Dexamethas one suppressed the LPS-induced TNF-alpha response of M phi, but no differen ce was detected between the M phi from the two strains. These results sugge st that endogenous MIF has no significant effect on the LPS-induced TNF-alp ha production and no effect on suppression of the response by glucocorticoi ds. Thus, MIF is not crucial for LPS-induced immune responses leading to sh ock.