Immunomodulation in community-acquired pneumonia

250 Pages·2013·8.6 MB·English

Immunomodulation in
community-acquired pneumonia
H.H.F. Remmelts
Immunomodulation in community-acquired pneumonia
Academic thesis, University of Utrecht, the Netherlands
ISBN: 978-90-393-5926-6
Cover and layout: R. Sanders
Printed by: Ten Brink, Meppel, the Netherlands
Copyright © H.H.F. Remmelts, the Netherlands, 2013. All rights reserved. No part
of this thesis may be reproduced, stored or transmitted, in any form or by any
means, without prior admission of the author. The copyright of the articles that
have been accepted for publication or that have been published are transferred
to the respective journals

Publication of this thesis was financially supported by: Raad van Bestuur and
Maatschap Internisten en MDL artsen, Ziekenhuis Gelderse Vallei Ede; Raad
van Bestuur and Maatschap Interne Geneeskunde, St. Antonius Ziekenhuis
Nieuwegein; Infection & Immunity Center Utrecht; Thermo Fisher Scientific;
Pfizer bv; Astellas Pharma B.V.
Immunomodulation in
community-acquired pneumonia
Modulatie van de immuunrespons bij een
buiten het ziekenhuis verworven longontsteking
(met een samenvatting in het Nederlands)
Proefschrift
ter verkrijging van de graad van doctor
aan de Universiteit Utrecht
op gezag van de rector magnificus, prof. dr. G.J. van der Zwaan,
ingevolge het besluit van het college voor promoties
in het openbaar te verdedigen
op vrijdag 31 mei 2013 des middags te 12.45 uur
door
Hilde Hilligje Femmigje Remmelts
geboren op 16 april 1984 te Kampen
Promotores: Prof. dr. D.H. Biesma
Prof. dr. G.T. Rijkers
Copromotores: Dr. J.J. Oosterheert
Dr. W.J.W. Bos
Voor mijn ouders
Beoordelingscommissie: Prof. dr. J.W.J. Lammers
Prof. dr. M.J.M. Bonten
Prof. dr. J.W.M. van der Meer
Prof. dr. J.G.J. van de Winkel
Prof. dr. M.M.E. Schneider
Paranimfen: Mw. M.D. Brons
Mw. L.J. Schijf

Contents
Chapter 1 General introduction, aims and outline of the thesis 11
Part I The immune response in community-acquired pneumonia 27
Chapter 2 Pathogen-specific inflammatory response patterns in 29
community-acquired pneumonia
Part II Immunomodulation by dexamethasone 49
Chapter 3 Dexamethasone and length of hospital stay in patients 51
with community-acquired pneumonia: a randomised,
double-blind, placebo-controlled trial
Chapter 4 Dexamethasone downregulates the systemic cytokine 73
response in patients with community-acquired
pneumonia
Chapter 5 Biomarkers define the clinical response to 87
dexamethasone in community-acquired pneumonia
Chapter 6 Changes in serum cortisol levels during community- 103
acquired pneumonia: the influence of dexamethasone
Part III Immunomodulation by macrolides 113
Chapter 7 Immunomodulatory effects of macrolides during 115
community-acquired pneumonia: a review of literature
Chapter 8 Adjuvant macrolides attenuate the pro-inflammatory 141
cytokine response to heat-killed Streptococcus
pneumoniae
Part IV Immunomodulation by vitamin D 157
Chapter 9 Addition of vitamin D status to prognostic scores 159
improves the prediction of outcome in community-
acquired pneumonia
Chapter 10 The role of vitamin D supplementation in the risk 177
of developing pneumonia: three independent case
control studies
Chapter 11 Summary, general discussion and perspectives 195
Summary for non-doctors (in Dutch) 219
List of co-authors 229
List of publications 235
Acknowledgements (in Dutch) 239
Curriculum vitae 247