Anti-inflammatory effects of the new generation synthetic surfactant CHF5633 on Ureaplasma-induced cytokine responses in human monocytes.
Synthetic surfactants represent a promising alternative to animal-derived preparations in the treatment of neonatal respiratory distress syndrome. The synthetic surfactant CHF5633 has proven biophysical effectiveness and, moreover, demonstrated anti-inflammatory effects in LPS-stimulated monocytes. With ureaplasmas being relevant pathogens in preterm lung inflammation, the present study addressed immunomodulatory features on Ureaplasma-induced monocyte cytokine responses.



Ureaplasma parvum-stimulated monocytes were exposed to CHF5633. TNF-α, IL-1β, IL-8, IL-10, TLR2 and TLR4 expression were analyzed using qPCR and flow cytometry.



CHF5633 did not induce pro-inflammation, and did not aggravate Ureaplasma-induced pro-inflammatory cytokine responses. It suppressed U. parvum-induced intracellular TNF-α (p < 0.05) and IL-1β (p < 0.05) in neonatal monocytes and inhibited Ureaplasma-induced TNF-α mRNA (p < 0.05), TNF-α protein (p < 0.001), and IL-1β (p = 0.05) in adult monocytes. Ureaplasma-modulated IL-8, IL-10, TLR2 and TLR4 were unaffected.



CHF5633 does neither act pro-apoptotic nor pro-inflammatory in native and Ureaplasma-infected monocytes. Suppression of Ureaplasma-induced TNF-α and IL-1β underlines anti-inflammatory features of CHF5633.
a University Children´s Hospital , University of Wuerzburg , Wuerzburg , Germany.
Kirsten
K
Glaser
a University Children´s Hospital , University of Wuerzburg , Wuerzburg , Germany.
Markus
M
Fehrholz
b Institute of Medical Microbiology and Hospital Hygiene , University Clinic of Heinrich-Heine University Duesseldorf , Duesseldorf , Germany.
Birgit
B
Henrich
c Institute for Hygiene and Microbiology , University of Wuerzburg , Wuerzburg , Germany.
Heike
H
Claus
d Department of Obstetrics and Gynecology , University of Wuerzburg , Wuerzburg , Germany.
Michael
M
Papsdorf
a University Children´s Hospital , University of Wuerzburg , Wuerzburg , Germany.
Christian P
CP
Speer
D000328:Adult; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D018929:Cell Culture Techniques; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005312:Fetal Blood / Q000166:cytology; D005434:Flow Cytometry; D064368:Healthy Volunteers; D006801:Humans; D007231:Infant, Newborn; D053583:Interleukin-1beta / Q000235:genetics / Q000276:immunology*; D009000:Monocytes / Q000187:drug effects* / Q000276:immunology; 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*; D012313:RNA / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000276:immunology*; D014509:Ureaplasma / Q000276:immunology*
D000893:Anti-Inflammatory Agents; C000592408:CHF5633; D053583:Interleukin-1beta; D010446:Peptide Fragments; D010713:Phosphatidylcholines; D037701:Pulmonary Surfactant-Associated Protein B; D037721:Pulmonary Surfactant-Associated Protein C; D014409:Tumor Necrosis Factor-alpha; D012313:RNA
Synthetic surfactant; Ureaplasma species; immunomodulation; lung inflammation; monocytes; preterm infants; respiratory distress syndrome