Endogenous leukemia inhibitory factor attenuates endotoxin response.

ABSTRACT

Leukemia inhibitory factor (LIF) is induced in inflammation and likely plays a regulatory role. Using LIF-deficient mice (LIF-/-), we report here that endogenous LIF has a protective role in endotoxic shock and host defence. LIF-/- mice have heightened sensitivity to LPS in a LPS/D-galactosamine (D-Gal) sensitization model compared to wild-type mice (LIF+/+), enhanced thrombocytopenia and leukopenia, with increased hepatic necrosis, neutrophil sequestration in the lung and accelerated mortality. These findings correlated with 10-fold higher tumour necrosis factor-alpha (TNFalpha) and interleukin-6 (IL-6) serum levels and reduced IL-10 production in LIF-/- mice in response to LPS. Therefore, endogenous LIF attenuates the endotoxic shock response, enhances the expression of basal acute phase proteins and IL-10 production, which downregulates TNFalpha synthesis and release and thereby confers partial protection to endotoxemia.