Adenosine increases during human experimental endotoxemia, but does not influence the immune response and subsequent organ injury

B Ramakers,P Pickkers,B Franke,H Hoeven,N Riksen

doi:10.1186/cc8243

Abstract

Although the innate immune response protects the host from invading pathogens, an excessive response may also lead to collateral damage to normal tissues. Adenosine has been proposed as an immunomodulator capable of inhibiting inflammation and preventing tissue injury. The C34T nonsense mutation in the AMP deaminase 1 (AMPD1) gene is thought to increase the endogenous adenosine concentration and has been associated with improved prognosis and survival in ischemic heart disease. Caffeine on the other hand, acting as a nonselective adenosine receptor antagonist, could diminish adenosine-mediated effects. The present study evaluated the endotoxemia-induced adenosine response, subclinical renal damage and endothelium dysfunction in healthy male subjects. Furthermore, we investigated whether the LPS-induced inflammatory response is attenuated by AMPD1 and enhanced by Caffeine, as well as its effects on markers of endothelium activation (plasma ICAM, VCAM) and renal damage (urinary excretion of GSTA1-1 and GSTP1-1).

Highlights

We previously showed that erythropoietin (EPO) attenuates the morphological signs of spinal cord ischemia/reperfusion (I/R) injury in swine [1] without, improving neurological function
The clinical use of EPO has been cautioned most recently due to serious safety concerns arising from an increased mortality in acute stroke patients treated with EPO and simultaneously receiving systemic thrombolysis [2]
Sodium 4-phenylbutyrate (PBA) has been reported to act as a chemical chaperone inhibiting Unfolded protein response (UPR)-mediated apoptosis triggered by ischemia in various organs other than the heart

Summary

Introduction

We previously showed that erythropoietin (EPO) attenuates the morphological signs of spinal cord ischemia/reperfusion (I/R) injury in swine [1] without, improving neurological function. Methods We studied 90 patients affected by severe sepsis or septic shock previously enrolled in a prospective trial regarding the impact of glycemic control on inflammation and coagulation. In a retrospective analysis of the data from the SBITS-trial [1] we investigated whether the initial level of serum IgG on admission to the hospital in patients with sepsis and septic shock (before the first administration of the first dose of intravenous immunoglobulins) could be seen as a prognostic parameter for the primary outcome, lethality on day 28, or the secondary endpoints, lethality on day 7 or on the ICU. The aim of this analysis was to assess the impact of real-time continuous glucose monitoring (CGM) on glucose variability in critically ill patients receiving intensive insulin therapy (IIT) Methods This is the post hoc analysis of a prospective, randomized, controlled trial [2]. Respecting anonymity we have statistically evaluated 103 replies (response rate was 13.8%) and compared with data from other European countries

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