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J Infect. 2019 Jan 23. pii: S0163-4453(19)30027-1. doi: 10.1016/j.jinf.2019.01.006. [Epub ahead of print]

Cytokine profiles in patients with Q fever fatigue syndrome.

Author information

1
Radboud Expertise Center for Q Fever, Department of Internal Medicine, Division of Infectious Diseases, Radboud University Medical Center, P.O. Box 9101, 6500 HB, Nijmegen, the Netherlands; Department of Internal Medicine, Radboud University Medical Center, P.O. Box 9101, 6500 HB, Nijmegen, the Netherlands. Electronic address: Ruud.Raijmakers@radboudumc.nl.
2
Department of Internal Medicine, Radboud University Medical Center, P.O. Box 9101, 6500 HB, Nijmegen, the Netherlands. Electronic address: Valerie.Koeken@radboudumc.nl.
3
Radboud Expertise Center for Q Fever, Department of Internal Medicine, Division of Infectious Diseases, Radboud University Medical Center, P.O. Box 9101, 6500 HB, Nijmegen, the Netherlands; Department of Internal Medicine, Radboud University Medical Center, P.O. Box 9101, 6500 HB, Nijmegen, the Netherlands. Electronic address: Anne.FM.Jansen@radboudumc.nl.
4
Radboud Expertise Center for Q Fever, Department of Internal Medicine, Division of Infectious Diseases, Radboud University Medical Center, P.O. Box 9101, 6500 HB, Nijmegen, the Netherlands; Department of Internal Medicine, Radboud University Medical Center, P.O. Box 9101, 6500 HB, Nijmegen, the Netherlands. Electronic address: Stephan.Keijmel@radboudumc.nl.
5
Department of Internal Medicine, Radboud University Medical Center, P.O. Box 9101, 6500 HB, Nijmegen, the Netherlands. Electronic address: Megan.Roerink@radboudumc.nl.
6
Radboud Expertise Center for Q Fever, Department of Internal Medicine, Division of Infectious Diseases, Radboud University Medical Center, P.O. Box 9101, 6500 HB, Nijmegen, the Netherlands; Department of Internal Medicine, Radboud University Medical Center, P.O. Box 9101, 6500 HB, Nijmegen, the Netherlands; Radboud Center for Infectious Diseases, Radboud University Medical Center, P.O. Box 9101, 6500 HB, Nijmegen, the Netherlands. Electronic address: Leo.Joosten@radboudumc.nl.
7
Radboud Expertise Center for Q Fever, Department of Internal Medicine, Division of Infectious Diseases, Radboud University Medical Center, P.O. Box 9101, 6500 HB, Nijmegen, the Netherlands; Department of Internal Medicine, Radboud University Medical Center, P.O. Box 9101, 6500 HB, Nijmegen, the Netherlands; Radboud Center for Infectious Diseases, Radboud University Medical Center, P.O. Box 9101, 6500 HB, Nijmegen, the Netherlands. Electronic address: Mihai.Netea@radboudumc.nl.
8
Radboud Expertise Center for Q Fever, Department of Internal Medicine, Division of Infectious Diseases, Radboud University Medical Center, P.O. Box 9101, 6500 HB, Nijmegen, the Netherlands; Department of Internal Medicine, Radboud University Medical Center, P.O. Box 9101, 6500 HB, Nijmegen, the Netherlands. Electronic address: Jos.vanderMeer@radboudumc.nl.
9
Radboud Expertise Center for Q Fever, Department of Internal Medicine, Division of Infectious Diseases, Radboud University Medical Center, P.O. Box 9101, 6500 HB, Nijmegen, the Netherlands; Department of Internal Medicine, Radboud University Medical Center, P.O. Box 9101, 6500 HB, Nijmegen, the Netherlands; Radboud Center for Infectious Diseases, Radboud University Medical Center, P.O. Box 9101, 6500 HB, Nijmegen, the Netherlands. Electronic address: Chantal.Bleeker-Rovers@radboudumc.nl.

Abstract

BACKGROUND:

Q fever fatigue syndrome (QFS) is a state of prolonged fatigue following around 20% of acute Q fever cases. It is thought that chronic inflammation plays a role in its etiology. To test this hypothesis we measured circulating cytokines and the ex-vivo cytokine production in patients with QFS and compared with various control groups.

MATERIALS/METHODS:

Peripheral blood mononuclear cells (PBMCs), whole blood, and serum were collected from 20 QFS patients, 19 chronic fatigue syndrome (CFS) patients, 19 Q fever seropositive controls, and 25 age- and sex-matched healthy controls. Coxiella-specific ex-vivo production of tumor necrosis factor (TNF)α, interleukin (IL)-1β, IL-6, and interferon (IFN) was measured, together with a total of 92 circulating inflammatory proteins.

RESULTS:

PBMCs of QFS patients produced more IL-6 (P = 0.0001), TNFα (P = 0.0002), and IL-1β (P = 0.0005) than the various control groups when stimulated with Coxiella antigen. QFS patients had distinct differences in circulating inflammatory markers compared to the other groups, including higher concentrations of circulating IL-6 and IFNγ.

CONCLUSION:

QFS patients showed signs of chronic inflammation compared to asymptomatic Q fever seropositive controls, CFS patients, and healthy controls, of which the monocyte-derived cytokines TNFα, IL-1β, and especially IL-6, are likely crucial components.

KEYWORDS:

CFS, chronic fatigue syndrome; IFNγ; IL-1β; IL-6; Proximity Extension Assay; QFS, Q fever fatigue syndrome; TNFα; cytokines

PMID:
30684502
DOI:
10.1016/j.jinf.2019.01.006

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