The mechanism by which interleukin-1 beta reduces net fluid absorption from the rat colon

IL-1β is suspected to be involved in the diarrhea that always accompanies inflammatory bowel disease. This work was aimed at studying the in vivo effect of IL-1β on the net absorption of fluid, Na⁺ and Cl^- from the rat colon, and at delineating its mechanism of action. Rats were injected i.p. with IL-1β (1 μg/kg body weight) and the colon was perfused, four hours later, with Krebs-Ringer buffer. Net fluid absorption was calculated as the difference between the total volume of the buffer infused and collected per cm² of perfused intestine. Chloride in both buffers was determined by titration according to Mohr's method and net Cl^- absorption was calculated in the same way. IL-1β reduced the net absorption of water and chloride. The cytokine also reduced the percentage recovery of the Na⁺-K⁺ ATPase activity in crude homogenates of membranes from surface and crypt colonic cells as revealed by the determination of inorganic phosphate released. In addition IL-1β decreased the protein expression of the Na⁺-K⁺ pump and increased that of the NaKCl₂ symporter. It is concluded that IL-1β has a dual effect: it inhibits the Na⁺-K⁺ pump and consequently NaCl absorption, and up-regulates the NaKCl₂ transporter and increases Cl^- secretion. The ultimate effect of the two processes is a net decrease in Na⁺+ and Cl^- absorption and an increase in water retention in the colon leading to the observed diarrhea in inflammatory bowel disease.