Cytokine expression during early and late phase of acute Puumala hantavirus infection

Mahmoud Sadeghi,Volker Daniel,Gerhard Opelz,Ulrich Burkhardt,Isabella Eckerle,Paul Schnitzler

doi:10.1186/1471-2172-12-65

Mahmoud Sadeghi, Volker Daniel + Show 4 more

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https://doi.org/10.1186/1471-2172-12-65

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Journal: BMC immunology	Publication Date: Nov 16, 2011
Citations: 102	License type: cc-by

Affiliation: Heidelberg University, University of Bonn

Abstract

BackgroundHantaviruses of the family Bunyaviridae are emerging zoonotic pathogens which cause hemorrhagic fever with renal syndrome (HFRS) in the Old World and hantavirus pulmonary syndrome (HPS) in the New World. An immune-mediated pathogenesis is discussed for both syndromes. The aim of our study was to investigate cytokine expression during the course of acute Puumala hantavirus infection.ResultsWe retrospectively studied 64 patients hospitalised with acute Puumala hantavirus infection in 2010 during a hantavirus epidemic in Germany. Hantavirus infection was confirmed by positive anti-hantavirus IgG/IgM. Cytokine expression of IL-2, IL-5, IL-6, IL-8, IL-10, IFN-γ, TNF-α and TGF-β1 was analysed by ELISA during the early and late phase of acute hantavirus infection (average 6 and 12 days after onset of symptoms, respectively). A detailed description of the demographic and clinical presentation of severe hantavirus infection requiring hospitalization during the 2010 hantavirus epidemic in Germany is given. Acute hantavirus infection was characterized by significantly elevated levels of IL-2, IL-6, IL-8, TGF-β1 and TNF-α in both early and late phase compared to healthy controls. From early to late phase of disease, IL-6, IL-10 and TNF-α significantly decreased whereas TGF-β1 levels increased. Disease severity characterized by elevated creatinine and low platelet counts was correlated with high pro-inflammatory IL-6 and TNF-α but low immunosuppressive TGF-β1 levels and vice versa .ConclusionHigh expression of cytokines activating T-lymphocytes, monocytes and macrophages in the early phase of disease supports the hypothesis of an immune-mediated pathogenesis. In the late phase of disease, immunosuppressive TGF-β1 level increase significantly. We suggest that delayed induction of a protective immune mechanism to downregulate a massive early pro-inflammatory immune response might contribute to the pathologies characteristic of human hantavirus infection.

Highlights

Hantaviruses of the family Bunyaviridae are emerging zoonotic pathogens which cause hemorrhagic fever with renal syndrome (HFRS) in the Old World and hantavirus pulmonary syndrome (HPS) in the New World
Most clinical studies indicate an important role of pro-inflammatory cytokines in the immunopathogenesis of HFRS/HPS [9,10,11]
Endothelial cells, monocytes and macrophages as well as platelets can be a rich source of cytokines/chemokines during the infection with hantavirus and contribute to the HFRS/HPS immunopathogenesis [9,10,11,12]

Summary

Introduction

Hantaviruses of the family Bunyaviridae are emerging zoonotic pathogens which cause hemorrhagic fever with renal syndrome (HFRS) in the Old World and hantavirus pulmonary syndrome (HPS) in the New World. Hantaviruses of the family Bunyaviridae are emerging zoonotic pathogens which cause two distinct syndromes in humans: hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS) [1,2,3]. Immunopathogenesis of both syndromes is characterized by increased vascular permeability resulting in severe capillary leakage and hemorrhagic diathesis. Most data are from patients with HFRS/HPS, immunohistochemical staining and gene polymorphism studies showed an association of pro-inflammatory cytokines and disease in PUUV infection with significantly elevated serum levels of TNF-a, IL-6, IL-2 and IFN-g in blood and urine [2,14,15]

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