Anti-inflammatory effects of the new generation synthetic surfactant CHF5633 on Ureaplasma-induced cytokine responses in human monocytes

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-, IL-1, 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- (p<0.05) and IL-1 (p<0.05) in neonatal monocytes and inhibited Ureaplasma-induced TNF- mRNA (p<0.05), TNF- protein (p<0.001), and IL-1 (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- and IL-1 underlines anti-inflammatory features of CHF5633.