Interleukin-1_β increases urine flow rate and inhibits protein expression of Na⁺/K⁺-ATPase in the rat jejunum and kidney

The effect of interleukin-1_β (IL-1_β) on urine flow rates and Na⁺/K⁺-ATPase activity and expression was studied in rat intestinal and renal epithelia. The cytokine produced a significant diuretic effect and increased urine flow rate by around 10-fold compared with the control. This effect was considered to be secondary to the well-documented natriuretic effect of the cytokine described in the literature. On the other hand, we have shown previously that IL-1_β inhibits glucose absorption from the jejunum. As sodium excretion and glucose absorption are both dependent on Na⁺/K⁺-ATPase activity, the effect of the cytokine on the renal and intestinal pump was investigated. IL-1_β inhibited, in a dose-dependent manner, the activity of Na⁺/K⁺-ATPase in villus and crypt jejunal cells and in medullary and cortical kidney cells. Western blot analysis revealed a decrease in the protein expression of the enzyme, which was confirmed by the radiolabeled ouabain binding assay. The results suggest that the diuretic and natriuretic effect of IL-1_β and its inhibitory effect on glucose absorption are all due to downregulation of the Na⁺/K⁺ pump in the kidney and jejunum.