Regulation of glucose metabolism after endotoxin and during infection is largely independent of endogenous tumor necrosis factor.

Increased hepatic glucose production and glucose utilization involving multiple tissues occur in response to administration of bacterial lipopolysaccharide (LPS) and are metabolic hallmarks of hypermetabolic sepsis. As a proximal mediator in the host response to infection-like challenges, tumor necrosis factor (TNF) may enhance glucose metabolism by directly interacting with cells or by initiating a cascade of events leading to changes in glucose production and utilization. To determine if endogenous TNF is an important mediator in LPS- or sepsis-induced changes in glucose metabolism, rats were pretreated with a neutralizing goat anti-TNF IgG antibody prior to intravenous LPS or subcutaneous live Escherichia coli administration. Whereas high levels of plasma TNF were observed in rats not pretreated with anti-TNF, TNF was not detected 90 min after LPS in rats receiving the antibody. Pretreatment with anti-TNF attenuated the increase in plasma lactate and glucagon levels in LPS-challenged rats but failed to ameliorate the LPS-induced hyperglycemia and increase in glucose rate of appearance (Ra). The LPS-stimulated increase of in vivo glucose metabolic rate (Rg) of examined tissues, measured with [14C]-2-deoxyglucose, was not altered by anti-TNF. Likewise, rats treated with anti-TNF prior to induction of hypermetabolic infection exhibited usual increases in whole-body glucose Ra and metabolic clearance rate. Although neutralizing TNF failed to prevent the sepsis-induced augmentation of Rg in any tissue examined, it reduced the increase in the lung (P < 0.05) and tended to decrease it in other barrier tissues as well as in the spleen.(ABSTRACT TRUNCATED AT 250 WORDS)