Circulating Concentrations of Adiponectin, an Endogenous Lipopolysaccharide Neutralizing Protein, Decrease in Rats with Polymicrobial Sepsis

Abstract

Adiponectin is an anti-inflammatory cytokine that is specifically and abundantly produced by adipocytes as a secretory protein. A direct interaction between adiponectin and lipopolysaccharide (LPS) is not fully understood. To elucidate the effects of adiponectin on LPS, we first investigated interactions between recombinant adiponectin and LPS. Various concentrations of LPS (50, 500, and 5000 pg/ml) and recombinant adiponectin (1, 10, and 100 microg/ml) were incubated for 1 h. The limulus amoebocyte lysate (LAL) activities in the mixture were measured. Interactions between adiponectin (100 microg/ml) and LPS (100 and 300 microg/ml) were also analyzed in Western blotting. Next, we determined plasma adiponectin, tumor necrosis factor-alpha (TNF-alpha), and endotoxin levels at 1.5, 3, and 24 h after onsets of rodent polymicrobial sepsis induced by cecal ligation and puncture (CLP). The incubation with adiponectin significantly and dose-dependently suppressed LAL activity in the mixture compared to control. Western blotting revealed that adiponectin incubated with LPS shifted to a higher mass. In the animal model of sepsis, both plasma endotoxin and TNF-alpha levels after CLP gradually increased and were significantly higher at 3, 24 h compared to those after sham operation. On the contrary, plasma adiponectin levels after CLP gradually decreased and were significantly lower at 3, 24 h compared to those after sham operation. Plasma adiponectin levels were negatively correlated with plasma endotoxin levels (r = -0.77, P < 0.01). Our results indicate that adiponectin might neutralize LPS in vitro and diminish LPS activity in rats with polymicrobial sepsis. These findings suggest that the anti-inflammatory effects of adiponectin are in part likely because of neutralization of LPS activity.