title: The new generation synthetic reconstituted surfactant CHF5633 suppresses LPS-induced cytokine responses in human neonatal monocytes.
abstract: New generation synthetic surfactants represent a promising alternative in the treatment of respiratory distress syndrome in preterm infants. CHF5633, a new generation reconstituted agent, has demonstrated biophysical effectiveness in vitro and in vivo. In accordance to several well-known surfactant preparations, we recently demonstrated anti-inflammatory effects on LPS-induced cytokine responses in human adult monocytes. The present study addressed pro- and anti-inflammatory effects of CHF5633 in human cord blood monocytes.
  
  
  
  Purified neonatal CD14(+) cells, either native or simultaneously stimulated with E. coli LPS, were exposed to CHF5633. TNF-α, IL-1β, IL-8 and IL-10 as well as TLR2 and TLR4 expression were analyzed by means of real-time quantitative PCR and flow cytometry.
  
  
  
  CHF5633 did not induce pro-inflammation in native human neonatal monocytes and did not aggravate LPS-induced cytokine responses. Exposure to CHF5633 led to a significant decrease in LPS-induced intracellular TNF-α protein expression, and significantly suppressed LPS-induced mRNA and intracellular protein expression of IL-1β. CHF5633 incubation did not affect cell viability, indicating that the suppressive activity was not due to toxic effects on neonatal monocytes. LPS-induced IL-8, IL-10, TLR2 and TLR4 expression were unaffected.
  
  
  
  Our data confirm that CHF5633 does not exert unintended pro-apoptotic and pro-inflammatory effects in human neonatal monocytes. CHF5633 rather suppressed LPS-induced TNF-α and IL-1β cytokine responses. Our data add to previous work and may indicate anti-inflammatory features of CHF5633 on LPS-induced monocyte cytokine responses.
authors: University Children's Hospital, University of Wuerzburg, Germany. Electronic address: Glaser_K@ukw.de.
authors: Kirsten
authors: K
authors: Glaser
authors: University Children's Hospital, University of Wuerzburg, Germany.
authors: Markus
authors: M
authors: Fehrholz
authors: Department of Obstetrics and Gynecology, University of Wuerzburg, Germany.
authors: Michael
authors: M
authors: Papsdorf
authors: Department of Molecular Medicine and Surgery, Karolinska Institutet at Karolinska, University Hospital, Stockholm, Sweden.
authors: Tore
authors: T
authors: Curstedt
authors: University Children's Hospital, University of Wuerzburg, Germany.
authors: Steffen
authors: S
authors: Kunzmann
authors: University Children's Hospital, University of Wuerzburg, Germany.
authors: Christian P
authors: CP
authors: Speer
mesh_terms: D016207:Cytokines / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000276:immunology; D005312:Fetal Blood / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D005434:Flow Cytometry; D006801:Humans; D007231:Infant, Newborn; D016753:Interleukin-10 / Q000235:genetics; D053583:Interleukin-1beta / Q000235:genetics; D016209:Interleukin-8 / Q000235:genetics; D018950:Lipopolysaccharide Receptors / Q000235:genetics; D008070:Lipopolysaccharides / Q000276:immunology*; D009000:Monocytes / Q000276:immunology* / Q000378:metabolism; D010446:Peptide Fragments / Q000494:pharmacology*; D010713:Phosphatidylcholines / Q000494:pharmacology*; D037701:Pulmonary Surfactant-Associated Protein B / Q000494:pharmacology*; D037721:Pulmonary Surfactant-Associated Protein C / Q000494:pharmacology*; D060888:Real-Time Polymerase Chain Reaction; D012127:Respiratory Distress Syndrome, Newborn / Q000188:drug therapy; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4 / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
chemical_list: C000592408:CHF5633; D016207:Cytokines; C508609:IL10 protein, human; D053583:Interleukin-1beta; D016209:Interleukin-8; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; D010446:Peptide Fragments; D010713:Phosphatidylcholines; D037701:Pulmonary Surfactant-Associated Protein B; D037721:Pulmonary Surfactant-Associated Protein C; C495342:TLR2 protein, human; C495345:TLR4 protein, human; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10
keywords: Immunomodulation; Lung inflammation; Neonatal monocytes; Respiratory distress syndrome; Synthetic surfactant