Sepsis in rats stimulates cellular proliferation in the mucosa of the small intestine.

BACKGROUND/AIMS: Increased protein synthesis in intestinal mucosa during sepsis may reflect increased cell turnover. The influence of sepsis and endotoxemia on cellular proliferation in the mucosa of the small intestine was studied.

METHODS

Sepsis was induced in rats by cecal ligation and puncture. Control rats were sham-operated. Other rats were treated with endotoxin (total dose, 2 mg/kg), human recombinant tumor necrosis factor alpha, or human recombinant interleukin 1 alpha at a dose of 100 micrograms/kg each. Villus height and crypt depth in the jejunum were measured as the number of cells along the side of the villus and crypt, respectively. Cellular proliferation was assessed by measuring the rate of [3H]thymidine incorporation into DNA of the jejunal mucosa and performing autoradiographic studies after intravenous administration of [3H]thymidine.

RESULTS

Sepsis resulted in reduced villus height, increased crypt depth, and increased incorporation of [3H]thymidine into DNA in the jejunal mucosa. Autoradiography after administration of [3H]thymidine showed labeled cells almost exclusively in the crypts; the number of labeled cells per crpt was higher in septic than in control rats. Administration of endotoxin or recombinant interleukin 1 alpha, but not recombinant tumor necrosis factor alpha, stimulated the incorporation of [3H]-thymidine into DNA in the jejunal mucosa.

CONCLUSION

Sepsis and endotoxemia stimulate cellular proliferation in the mucosa of the small intestine. This response to sepsis and endotoxemia may be partly mediated by interleukin 1.