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Anti-inflammatory effects of the new generation synthetic surfactant CHF5633 on Ureaplasma-induced cytokine responses in human monocytes
Authors:Kirsten Glaser  Markus Fehrholz  Birgit Henrich  Heike Claus  Michael Papsdorf  Christian P Speer
Institution:1. University Children′s Hospital, University of Wuerzburg, Wuerzburg, Germany;2. Institute of Medical Microbiology and Hospital Hygiene, University Clinic of Heinrich-Heine University Duesseldorf, Duesseldorf, Germany;3. Institute for Hygiene and Microbiology, University of Wuerzburg, Wuerzburg, Germany;4. Department of Obstetrics and Gynecology, University of Wuerzburg, Wuerzburg, Germany
Abstract:Background: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

Keywords:Synthetic surfactant  respiratory distress syndrome  lung inflammation  Ureaplasma species  immunomodulation  preterm infants  monocytes
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