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Nutritional Immunology

Kupffer Cell Activity Is Involved in the Hepatoprotective Effect of Dietary Oligofructose in Rats with Endotoxic Shock

Unit of Pharmacokinetics, Metabolism, Nutrition and Toxicology, School of Pharmacy, Université Catholique de Louvain, B-1200 Brussels, Belgium

¹To whom correspondence should be addressed. E-mail: delzenne{at}pmnt.ucl.ac.be.

In the present study, we tested the hypothesis that dietary oligofructose (FOS) can modulate both the response to an endotoxic shock induced by lipopolysaccharide (LPS) administration and the activity of resident hepatic macrophages, i.e., Kupffer cells. Male Wistar rats (n = 5–9 per group) were fed a standard diet or a diet supplemented with 10 g/100 g FOS for 3 wk. LPS (10 mg/kg) or saline were injected i.p. after dietary treatment. After LPS injection, serum levels of tumor necrosis factor (TNF)-, a proinflammatory cytokine, and prostaglandin E₂ (PGE₂), an immunosuppressive mediator, were higher in FOS-treated rats than in control rats. Alanine aminotransferase (ALT) activity was 50% lower than in controls 24 h after LPS administration in FOS-treated rats, suggesting less hepatic injury; this was confirmed through histological analysis. FOS treatment increased the number of large phagocytic Kupffer cells, as assessed by histological examination of the liver after colloidal carbon injection into the portal vein. Precision-cut liver slices (PCLS) from FOS-treated rats released more TNF- and PGE₂ into the incubation medium than PCLS from control rats, independently of LPS challenge in vitro. This would suggest that the higher Kupffer cell phagocytic activity and secretion capacity due to FOS supplementation improve LPS clearance in liver tissue and reduce hepatocyte alterations. This study supports the hypothesis that oligofructose might decrease liver tissue injury after endotoxic shock and sepsis.

KEY WORDS: • Kupffer cells • sepsis • oligofructose • precision-cut liver slices • lipopolysaccharide

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