BACKGROUND: Catabolism and weight loss are serious problems in patients with active inflammatory bowel disease (IBD). The body nitrogen (N) depletion is partly related to increased hepatic capacity for the elimination of N through urea synthesis. This is probably caused by the inflammation per se, and the treatment with prednisolone may aggravate the problem, whereas the effect of biological therapy is unknown. Therefore, we examined the effects of prednisolone or infliximab on the regulation of urea synthesis in patients with active IBD. METHODS: Urea synthesis was quantified by the functional hepatic nitrogen clearance (FHNC), i.e., the slope of the linear relationship between the urea nitrogen synthesis rate and the blood α-amino nitrogen concentration during alanine infusion. Thirty-seven patients with active IBD treated with either prednisolone or infliximab were examined before and after 7 days of treatment. RESULTS: At baseline, the FHNC was similar in the 2 treatment groups (36 L/h). After 7 days, prednisolone increased the FHNC by 40% (55 L/h) (P = 0.03), whereas infliximab tended to reduce the FHNC by 15% (30 L/h) (P = 0.09). The changes in the FHNC differed significantly between the 2 treatment groups (P < 0.01). CONCLUSIONS: Prednisolone treatment further upregulated urea synthesis, which increases the hepatic loss of nitrogen and promotes body catabolism. In contrast, infliximab treatment caused no such aggravation and likely reduced the N loss. These results may argue in favor of infliximab therapy for IBD and add to the pathophysiological understanding of the interplay between inflammation, catabolism, and anti-inflammatory treatment.
BACKGROUND: Catabolism and weight loss are serious problems in patients with active inflammatory bowel disease (IBD). The body nitrogen (N) depletion is partly related to increased hepatic capacity for the elimination of N through urea synthesis. This is probably caused by the inflammation per se, and the treatment with prednisolone may aggravate the problem, whereas the effect of biological therapy is unknown. Therefore, we examined the effects of prednisolone or infliximab on the regulation of urea synthesis in patients with active IBD. METHODS:Urea synthesis was quantified by the functional hepatic nitrogen clearance (FHNC), i.e., the slope of the linear relationship between the ureanitrogen synthesis rate and the blood α-amino nitrogen concentration during alanine infusion. Thirty-seven patients with active IBD treated with either prednisolone or infliximab were examined before and after 7 days of treatment. RESULTS: At baseline, the FHNC was similar in the 2 treatment groups (36 L/h). After 7 days, prednisolone increased the FHNC by 40% (55 L/h) (P = 0.03), whereas infliximab tended to reduce the FHNC by 15% (30 L/h) (P = 0.09). The changes in the FHNC differed significantly between the 2 treatment groups (P < 0.01). CONCLUSIONS:Prednisolone treatment further upregulated urea synthesis, which increases the hepatic loss of nitrogen and promotes body catabolism. In contrast, infliximab treatment caused no such aggravation and likely reduced the N loss. These results may argue in favor of infliximab therapy for IBD and add to the pathophysiological understanding of the interplay between inflammation, catabolism, and anti-inflammatory treatment.