Changes in the natural abundance of ¹³CO₂/¹²CO₂ in breath due to lipopolysacchride-induced acute phase response

Abstract

The natural abundance of carbon-13 in blood proteins increases during the cachectic state and may be a biomarker for disease status. We hypothesized a corresponding drop in the relative abundance of ¹³C in breath CO₂. Using the lipopolysacchride (LPS)-induced endotoxemia model of the acute cachectic state, we demonstrated that the acute phase response causes shifts in the stable isotopes of carbon in exhaled CO₂ (¹³CO₂/¹²CO₂ delta value) shortly after administration of LPS while glucocorticoid treatment does not. Mice were injected with LPS and stable isotopes of blood amino acids and carbon in exhaled CO₂ were monitored. An increase in the relative isotopic mass of serum alanine, proline and threonine was observed at 3 h after LPS injection. Breath delta values began dropping immediately after administration of LPS, and were 4–5 delta values lower than those of the control animals by 2.5 h after injection. A corresponding drop in delta value was not observed with dexamethasone treatment. Thus protein synthesis during the acute phase response probably caused the fractionation of stable isotopes observed in the plasma amino acids and in exhaled breath ¹³CO₂ delta values. The exhaled breath ¹³CO₂ delta value may be a valuable real-time biomarker of cachexia associated with an acute phase response due to endotoxemia. Copyright © 2009 John Wiley & Sons, Ltd.