Tumor necrosis factor-α acutely up-regulates urea synthesis in vivo in rats – a hepatic component of inflammatory catabolism?

Abstract

Background. Catabolism is a serious problem in patients with active inflammation. The tissue nitrogen (N) depletion is related to increased hepatic capacity for elimination of N via conversion of amino-N into urea-N. This is caused by the inflammatory process, but the mediators responsible are unknown. Tumor necrosis factor-α (TNF-α) plays a key role in inflammation, and we hypothesized that TNF-α up-regulates urea synthesis. Methods. We examined the in vivo capacity of urea-N synthesis (CUNS) and mRNA levels of urea cycle enzyme genes 3 h after TNF-α injection in rats. Circulating concentrations of glucagon, corticosterone, insulin, glucose, cytokines and acute phase proteins and their liver tissue gene expressions were measured. Results. TNF-α increased CUNS by 40% (p=0.03) despite decreased urea-cycle enzyme gene expression. TNF-α increased interleukin 6 (IL-6) (p < 0.001); circulating acute phase proteins were unchanged. Conclusion. TNF-α in rats caused an acute up-regulation of the in vivo capacity of urea synthesis which may promote loss of nitrogen from the body and catabolism. The results indicate that TNF-α has a post-transcriptional effect on regulation of urea synthesis that is independent of the acute phase protein synthesis. Effects of IL-6 may be involved.