title: Inflammatory Characteristics of Monocytes from Pediatric Patients with Tuberous Sclerosis.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Pediatric Immunology, Children's Hospital, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany.
authors.forename: Claudius U
authors.initials: CU
authors.lastname: Meyer
authors.affiliation: Children's Hospital of the University Medical Center, Münster, Germany.
authors.forename: Gerhard
authors.initials: G
authors.lastname: Kurlemann
authors.affiliation: Medizinische Klinik und Poliklinik IV, Klinikum d. Universität München, Munich, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Sauter
authors.affiliation: Epilepsy Center, Kork-Kehl, Germany.
authors.forename: Adelheid
authors.initials: A
authors.lastname: Wiemer-Kruel
authors.affiliation: Children's Hospital of the University Medical Center, Gießen, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Hahn
authors.affiliation: Pediatric Immunology, Children's Hospital, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany.
authors.forename: Aysefa
authors.initials: A
authors.lastname: Doganci
authors.affiliation: Pediatric Immunology, Children's Hospital, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Birkholz
authors.affiliation: Pediatric Immunology, Children's Hospital, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany.
authors.forename: Jörg
authors.initials: J
authors.lastname: Faber
authors.affiliation: Pediatric Immunology, Children's Hospital, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany.
authors.forename: Stephan
authors.initials: S
authors.lastname: Gehring
authors.affiliation: DBZ, Vivantes Klinikum Neukölln, Berlin, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Hertzberg
authors.affiliation: Pediatric Immunology, Children's Hospital, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany.
authors.forename: Fred
authors.initials: F
authors.lastname: Zepp
authors.affiliation: Children's Hospital of the Dr. Horst-Schmidt-Kliniken, Wiesbaden, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Knuf
mesh_terms: D002648:Child; D002675:Child, Preschool; D003430:Cross-Sectional Studies; D016207:Cytokines / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology; D007223:Infant; D007231:Infant, Newborn; D007249:Inflammation / Q000235:genetics / Q000378:metabolism*; D018836:Inflammation Mediators / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism*; D020123:Sirolimus / Q000494:pharmacology; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D014402:Tuberous Sclerosis / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*
chemical_list: D016207:Cytokines; D007166:Immunosuppressive Agents; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus