IL-6 has no acute effect on the regulation of urea synthesis in vivo in rats

Abstract

Background. Clinical or experimentally induced, active inflammation up-regulates the in vivo capacity of urea synthesis (CUNS), which promotes nitrogen removal from the body and metabolic catabolism. We have shown that tumor necrosis factor α (TNF-α) up-regulates CUNS and increases interleukin 6 expression (IL-6) within hours of administration. The described effect of TNF-α on nitrogen homeostasis may, therefore, depend on IL-6. Methods. Three hours after the i.v. injection of 125 μg.kg⁻¹ of IL-6 or placebo, we evaluated the CUNS, hepatocyte urea cycle enzyme protein levels and the mRNA levels of the urea cycle enzyme genes in rats. The prevailing rat serum acute phase proteins and their liver mRNA levels were also measured. Results. IL-6 did not change CUNS or hepatocyte urea cycle enzyme protein levels, whereas urea cycle enzyme mRNA levels, except for ornithine transcarbamylase (OTC), decreased by approximately 20%. The liver mRNA levels of α2MG, haptoglobin and α1AGP all increased by 1.5- to 2-fold (p < 0.001). In serum, only the α2MG concentration slightly increased (p < 0.001), whereas the levels of the other circulating acute phase proteins remained unchanged. Conclusion. IL-6 is not the mediator of the in vivo CUNS up-regulation observed 3 h after TNF-α administration, but it may be involved in the down-regulation of urea cycle genes. IL-6 may also mediate TNF-α effects on acute phase protein gene expression. Thus, IL-6 did not contribute to the in vivo hepatic component of inflammation-associated catabolism.

Key Words::

• Cytokines
• inflammation
• metabolism
• rats
• RNA
• messenger
• urea

Acknowledgements

This study was generously supported by grants from The Aarhus University Research Foundation, the Novo Nordic Foundation, and the Clinical Institute, Aarhus University, Denmark. We are indebted to Rikke Andersen, Birgitte Nielsen, Joan Hansen, Kirsten Nyborg and Kirsten Priisholm for their skilled technical assistance.

Declaration of interest: The authors report no conflict of interest. The authors alone are responsible for the content and writing of the article.