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Neuropediatrics 2015; 46(05): 335-343
DOI: 10.1055/s-0035-1562925
Original Article
Georg Thieme Verlag KG Stuttgart · New York

Inflammatory Characteristics of Monocytes from Pediatric Patients with Tuberous Sclerosis

Claudius U. Meyer
1   Pediatric Immunology, Children's Hospital, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany
,
Gerhard Kurlemann
2   Children's Hospital of the University Medical Center, Münster, Germany
,
Matthias Sauter
3   Medizinische Klinik und Poliklinik IV, Klinikum d. Universität München, Munich, Germany
,
Adelheid Wiemer-Kruel
4   Epilepsy Center, Kork-Kehl, Germany
,
Andreas Hahn
5   Children's Hospital of the University Medical Center, Gießen, Germany
,
Aysefa Doganci
1   Pediatric Immunology, Children's Hospital, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany
,
Julia Birkholz
1   Pediatric Immunology, Children's Hospital, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany
,
Jörg Faber
1   Pediatric Immunology, Children's Hospital, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany
,
Stephan Gehring
1   Pediatric Immunology, Children's Hospital, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany
,
Christoph Hertzberg
6   DBZ, Vivantes Klinikum Neukölln, Berlin, Germany
,
Fred Zepp
1   Pediatric Immunology, Children's Hospital, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany
,
Markus Knuf
7   Children's Hospital of the Dr. Horst-Schmidt-Kliniken, Wiesbaden, Germany
› Author Affiliations
Further Information

Publication History

23 December 2014

22 June 2015

Publication Date:
10 September 2015 (online)

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Abstract

Objective Therapeutic options for the tuberous sclerosis complex (TSC) syndrome showed varying outcomes. Malfunctional tsc1/tsc2 genes leave mTOR uninhibited, a positive downstream modulator of the innate proinflammatory immune system, which has not yet been described in pediatric patients with TSC.

Methods Using polymerase chain reaction (PCR) gene expression levels of monocytes after cultivation with lipopolysaccharide (LPS) or with LPS + mTOR inhibitor rapamycin, patients with TSC (n = 16) were compared with healthy subjects (n = 20).

Results Compared with monocytes from healthy controls, LPS showed a more prominent gene expression pattern in patients with TSC (CCL24, CXCL10, IL-6, IL-10, and IL-1B). Proinflammatory reactions against LPS were modulated by rapamycin. With LPS + rapamycin monocytes from patients with TSC showed gene expression patterns different from healthy subjects. Furthermore, developmental differences were discernible in patients with TSC, compared with gene expression levels for patients 0 to 5 years to those 6 to 11 years of age, the latter with marked expression of IL-6 IL-1A, IL-1B, RIPK2, but also IL-10.

Conclusion The effects of LPS, even more of LPS with rapamycin on monocytes from patients with TSC suggested that inflammatory processes are distinct from those in healthy subjects. Furthermore, reaction to rapamycin indicates age-related gene expression levels. Our findings offer a model to decipher the unknown and varying gene expression pattern induced by rapamycin.

Keywords

tuberous sclerosis - inflammation - rapamycin - monocyte - children

Supplementary Data

Supplementary data (Figs. S1 and S2, and Table S1) are available at: www.thieme-connect.com/products/ejournals/html/10.1055/s-0035-1562925.


Supplementary Material

 

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