Deficiency of the macrophage migration inhibitory factor gene has no significant effect on endotoxaemia

Abstract

SUMMARYBy targeted disruption of the MIF gene, we have established a mouse strain de®cient in macrophage (Mw) migration inhibitory factor (MIF). Despite previous reports indicating an essential role of MIF in endotoxaemia, an injection of lipopolysaccharide (LPS) into the MIF-de®cient mice (maintained under speci®c pathogen-free conditions) caused shock. No signi®cant difference was detected between the MIF-de®cient mutant and normal mice in susceptibility to LPS for endotoxaemia or tumour necrosis factor-a (TNF-a) formation upon LPS injection. Peritoneal Mw from the two strains produced TNF-a in response to LPS with similar dose responses. Dexamethasone suppressed the LPS-induced TNF-a response of Mw, but no difference was detected between the Mw from the two strains. These results suggest that endogenous MIF has no signi®cant effect on the LPS-induced TNF-a production and no effect on suppression of the response by glucocorticoids. Thus, MIF is not crucial for LPS-induced immune responses leading to shock.

Macrophage migration inhibitory factor contributes to development of nonsteroidal anti-inflammatory drugs-induced gastric injury in mice

“…MIF-deficient mice (bred onto a BALB/c background) were established as described previously [14]. All mice were maintained on standard laboratory chow and given food and water ad libitum.…”

CD4 cell-secreted, posttranslationally modified cytokine GIF suppresses Th2 responses by inhibiting the initiation of IL-4 production

“…The initial report of the mutant mice demonstrated a reduced rate of endotoxin shock (11). However, the same (14) and other (12) lines of the mutant mice later showed a normal sensitivity to LPS. Thus, the role of GIF in innate immunity needs to be reevaluated.…”

“…GIF-deficient mice have been generated and studied (11)(12)(13). They develop normal populations of haematopoietic cells.…”

“…To determine whether modified or unmodified GIF has any physiological relevance in the regulation of the Th2 immune response, we used a line of GIF-deficient mice (12) and found that GIF suppressed T-dependent antibody formation and allergic airway inflammation. The responsiveness of toll-like receptors (TLRs) to their ligands was not altered in GIF-deficient mice.…”

Natural killer T cells ameliorate antibody-induced arthritis in macrophage migration inhibitory factor transgenic mice

“…After the molecular cloning of the mif gene (2), it has become increasingly clear that MIF is a unique cytokine with various actions on many target cells (3,4). Recent studies, using genetically engineered animals such as MIF knockout (5,6) and MIF transgenic (MIF Tg ) (7,8) mice, have revealed the importance of MIF in inflammatory diseases.…”