Background: Sepsis develops when the initial, appropriate host response to an infection becomes amplified and subsequently dysregulated. Recent research has shown that the pathogenesis of sepsis can only partially be explained by an aberrant inflammatory response, metabolic deregulation also plays a vital role. Here we have investigated the role of a novel metabolite in sepsis pathophysiology.

Methods: Urine was obtained from an LPS mouse model of sepsis and human septic patients. A colorimetric assay and mass-spectroscopy were performed to determine the expression levels of metabolite X (mX). Furthermore, mice were implanted with radiotelemetry probes and the effect of supplementation with mX on clinical symptomology was determined. Following co-administration of LPS and mX real-time measurements of temperature, heart-rate and blood pressure were obtained.

Results: The urinary excretion of mX is significantly reduced in both a mouse model of LPS-induced sepsis, and in samples taken from human septic patients. Subsequent data showed that this is due to enhanced activation of the enzyme responsible for mX degradation. Moreover, co-administration of LPS and mX in mice modulates a number of aspects of physiological responses to sepsis, and in particular, protects against sepsis-induced hypothermia. The mechanism underlying this protective effect is due to suppressed nitric-oxide signalling.

Conclusion: Our results identify a novel role for mX in sepsis pathophysiology and suggest that this metabolite is a critical diagnostic and therapeutic target for sepsis. Future studies will fully elucidate the mechanisms underlying our observations.

mX not disclosed due to IP application but will be disclosed for presentation.

  • This is an open-access article distributed under the terms of the Creative Commons Attribution License.

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