title: TLR4 preconditioning is associated with low success of OK-432 treatment for lymphatic malformations in children.
abstract: OBJECTIVE
  We have recently shown that the relative TLR4 expression on monocytes of low responding pediatric patients after OK-432 treatment is significantly reduced after stimulation with lipopolysaccharide (LPS) compared with high responding children. The aim of this study was to perform further analysis to explain this observation.
  
  
  METHODS
  Monocytes from children with high (HR, n = 5) and low response (LR, n = 6) after previous OK-432 treatment were stimulated with LPS for 20 h and analyzed with fluorescence-activated cell sorting (mean fluorescence intensity, MFI; level of significance P ≤ 0.05).
  
  
  RESULTS
  Mean MFI after LPS stimulation was comparable in both groups (HR 1142 ± 652 units, LR 839 ± 427 units, P = 0.85). Significant changes after LPS stimulation are explained by higher pre-stimulation values in the LR group compared with the HR group (950 ± 718 vs. 477 ± 341, P = 0.25) with considerable differences of the mean expression changes after LPS stimulation (HR 665 ± 683 vs. LR -111 ± 605, P = 0.08).
  
  
  CONCLUSIONS
  The previously shown reduced TLR4 upregulation on monocytes after LPS stimulation in the LR group compared with the HR group can be primarily explained by TLR preconditioning. This observation implies the use of absolute values with definite thresholds.
authors.affiliation: Department of Pediatric Surgery, Charité - Universitätsmedizin Berlin, 13353, Berlin, Germany. marc.reismann@charite.de.|Department of Pediatric Surgery, Astrid Lindgrens Children´s Hospital, Karolinska University Hospital, 17176, Stockholm, Sweden. marc.reismann@charite.de.|Unit of Pediatric Surgery, Department of Women´s and Children´s Health, Karolinska Institutet, 17176, Stockholm, Sweden. marc.reismann@charite.de.
authors.forename: Marc
authors.initials: M
authors.lastname: Reismann
authors.affiliation: Department of Pediatric Surgery, Astrid Lindgrens Children´s Hospital, Karolinska University Hospital, 17176, Stockholm, Sweden.|Unit of Pediatric Surgery, Department of Women´s and Children´s Health, Karolinska Institutet, 17176, Stockholm, Sweden.
authors.forename: Nader
authors.initials: N
authors.lastname: Ghaffarpour
authors.affiliation: Translational Immunology Unit, Department of Medicine, Karolinska Institutet, 17176, Stockholm, Sweden.
authors.forename: Ethel
authors.initials: E
authors.lastname: Luvall
authors.affiliation: Clinic for Peadiatric Pneumology and Neonatology, Hannover Medical School, 30625, Hannover, Germany.
authors.forename: Adan
authors.initials: A
authors.lastname: Jirmo
authors.affiliation: Department of Pediatric Surgery, Charité - Universitätsmedizin Berlin, 13353, Berlin, Germany.
authors.forename: Josephine
authors.initials: J
authors.lastname: Radtke
authors.affiliation: Department of Pediatric Surgery, Astrid Lindgrens Children´s Hospital, Karolinska University Hospital, 17176, Stockholm, Sweden.|Unit of Pediatric Surgery, Department of Women´s and Children´s Health, Karolinska Institutet, 17176, Stockholm, Sweden.
authors.forename: Gösta
authors.initials: G
authors.lastname: Claesson
authors.affiliation: Department of Pediatric Surgery, Astrid Lindgrens Children´s Hospital, Karolinska University Hospital, 17176, Stockholm, Sweden.|Unit of Pediatric Surgery, Department of Women´s and Children´s Health, Karolinska Institutet, 17176, Stockholm, Sweden.
authors.forename: Tomas
authors.initials: T
authors.lastname: Wester
mesh_terms: D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007223:Infant; D008070:Lipopolysaccharides / Q000276:immunology*; D044148:Lymphatic Abnormalities / Q000276:immunology / Q000628:therapy*; D008297:Male; D009000:Monocytes / Q000276:immunology*; D010844:Picibanil / Q000008:administration & dosage* / Q000276:immunology; D012597:Sclerosing Solutions / Q000008:administration & dosage*; D051197:Toll-Like Receptor 4 / Q000096:biosynthesis* / Q000276:immunology
chemical_list: D008070:Lipopolysaccharides; D012597:Sclerosing Solutions; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D010844:Picibanil
keywords: Children; Lymphatic malformation; OK-432; Toll-like receptor