The new generation synthetic reconstituted surfactant CHF5633 suppresses LPS-induced cytokine responses in human neonatal monocytes

• Published in: Cytokine (Philadelphia, Pa.) Pa.), 2016-10, Vol.86, p.119-123
• Main Authors: Glaser, Kirsten, Fehrholz, Markus, Papsdorf, Michael, Curstedt, Tore, Kunzmann, Steffen, Speer, Christian P.
• Format: Article
• Language: English
• Subjects: Cytokines - antagonists & inhibitors; Cytokines - biosynthesis; Cytokines - immunology; Fetal Blood - cytology; Fetal Blood - drug effects; Fetal Blood - immunology; Flow Cytometry; Humans; Immunomodulation; Infant, Newborn; Interleukin-10 - genetics; Interleukin-1beta - genetics; Interleukin-8 - genetics; Lipopolysaccharide Receptors - genetics; Lipopolysaccharides - immunology; Lung inflammation; Medicin och hälsovetenskap; Monocytes - immunology; Monocytes - metabolism; Neonatal monocytes; Peptide Fragments - pharmacology; Phosphatidylcholines - pharmacology; Pulmonary Surfactant-Associated Protein B - pharmacology; Pulmonary Surfactant-Associated Protein C - pharmacology; Real-Time Polymerase Chain Reaction; Respiratory distress syndrome; Respiratory Distress Syndrome, Newborn - drug therapy; Synthetic surfactant; Toll-Like Receptor 2; Toll-Like Receptor 4 - genetics; Tumor Necrosis Factor-alpha - genetics
• ISSN: 1043-4666; 1096-0023; 1096-0023
• DOI: 10.1016/j.cyto.2016.08.004

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.