Monitoring of immune activation using biochemical changes in a porcine model of cardiac arrest.

Anton Amann,Hans-Ulrich Strohmenger,Josef Rieder,Viktoria Mayr,Herwig Antretter,Bernhard Widner,Dietmar Fuchs,Georg Hoffmann

doi:10.1080/09629350120102370

Anton Amann, Hans-Ulrich Strohmenger + Show 6 more

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https://doi.org/10.1080/09629350120102370

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Abstract

In animal models, immune activation is often difficult to assess because of the limited availability of specific assays to detect cytokine activities. In human monocytes/macrophages, interferon-gamma induces increased production of neopterin and an enhanced activity of indoleamine 2,3-dioxygenase, which degrades tryptophan via the kynurenine pathway. Therefore, monitoring of neopterin concentrations and of tryptophan degradation can serve to detect the extent of T helper cell 1-type immune activation during cellular immune response in humans. In a porcine model of cardiac arrest, we examined the potential use of neopterin measurements and determination of the tryptophan degradation rate as a means of estimating the extent of immune activation. Urinary neopterin concentrations were measured with high-performance liquid chromatography (HPLC) and radioimmunoassay (RIA) (BRAHMS Diagnostica, Berlin, Germany). Serum and plasma tryptophan and kynurenine concentrations were also determined using HPLC. Serum and urine neopterin concentrations were not detectable with HPLC in these specimens, whereas RIA gave weakly (presumably false) positive results. The mean serum tryptophan concentration was 39.0 +/- 6.2 micromol/l, and the mean kynurenine concentration was 0.85 +/- 0.33 micromol/l. The average kynurenine-per-tryptophan quotient in serum was 21.7 +/- 8.4 nmol/micromol, and that in plasma was 20.7 +/- 9.5 nmol/micromol (n = 7), which corresponds well to normal values in humans. This study provides preliminary data to support the monitoring of tryptophan degradation but not neopterin concentrations as a potential means of detecting immune activation in a porcine model. The kynurenine-per-tryptophan quotient may serve as a short-term measurement of immune activation and hence permit an estimate of the extent of immune activation.

Highlights

In animal models, immune activation is often difficult to assess because of the limited availability ofspecific assays to detect cytokine activities
Increased neopterin concentrations and an enhanced tryptophan degradation rate reflect the extent of T helper cell 1-type immune activation during cellular immune response in humans
This study provides preliminary data in support of the potential use of tryptophan degradation but not neopterin concentrations as immune activation markers in a porcine model

Summary

Introduction

Immune activation is often difficult to assess because of the limited availability of (species-)specific assays to detect cytokine activities. Measurement of neopterin in serum or urine has been established as a sensitive marker of cellular, i.e. T helper cell 1-type, immune response.[1] Neopterin is a stable, low-molecular mass compound (253 Da) produced in increased concentrations by interferon (IFN)-g-stimulated human and primate monocytes/ macrophages. In these cells, neopterin is produced at the expense of biopterin, because of a relative deficiency of 6-pyruvoyltetrahydropterin synthase (PTPS), the enzyme responsible for biosynthesis of 5,6,7,8-tetrahydrobiopterin. The clinical use of neopterin determination ranges from surveillance of allograft recipients for early detection of immunological complications in order to predict prognosis, to control of therapy in malignant diseases and HIV infection.[1,3]

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