Inflammation Research

, Volume 60, Issue 2, pp 127–135 | Cite as

In vitro testing for anti-inflammatory properties of compounds employing peripheral blood mononuclear cells freshly isolated from healthy donors

  • M. Jenny
  • M. Klieber
  • D. Zaknun
  • S. Schroecksnadel
  • K. Kurz
  • M. Ledochowski
  • H. Schennach
  • Dietmar Fuchs
Original Research Paper

Abstract

Introduction

Inflammation is crucially involved in a variety of diseases like autoimmune syndromes, cardiovascular and neurodegenerative disorders, cancer, sepsis and allograft rejection.

Methods

Freshly isolated human peripheral blood mononuclear cells (PBMCs) are used as a screening assay for anti-inflammatory properties of compounds. Determinations of neopterin production by ELISA and of tryptophan degradation by HPLC are used as read-outs. Results are compared with further markers of immune response and oxidative stress.

Results

Phytohaemagglutinin induced significant tryptophan degradation and neopterin formation in PBMC, which correlated with IFN-γ, TNF-α, soluble cytokine receptors and isoprostane-8. Addition of vitamin C and E suppressed the responses dose-dependently.

Discussion

The determination of tryptophan degradation and neopterin production in PBMC reflects various pro- and anti-inflammatory cascades that are of relevance also in patients. It constitutes a robust and reliable approach to screen anti-inflammatory or immunosuppressive drugs and may improve throughput, speed and cost-effectiveness in drug discovery.

Keywords

Tryptophan Kynurenine Indoleamine 2 3-Dioxygenase Neopterin Cytokine Cytokine receptors Interferon-γ 

Notes

Acknowledgments

The authors thank Miss Maria Gleinser for excellent technical assistance.

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Copyright information

© Springer Basel AG 2010

Authors and Affiliations

  • M. Jenny
    • 1
  • M. Klieber
    • 1
  • D. Zaknun
    • 4
  • S. Schroecksnadel
    • 1
  • K. Kurz
    • 2
  • M. Ledochowski
    • 2
  • H. Schennach
    • 3
  • Dietmar Fuchs
    • 1
  1. 1.Division of Biological Chemistry, BiocenterInnsbruck Medical UniversityInnsbruckAustria
  2. 2.Department of Internal MedicineInnsbruck Medical UniversityInnsbruckAustria
  3. 3.Institute for Blood Transfusion and ImmunologyUniversity ClinicsInnsbruckAustria
  4. 4.Department of PediatricsUniversity Hospital of ViennaViennaAustria

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