Pentoxifylline modulates LPS-induced hyperinflammation in monocytes of preterm infants in vitro

BACKGROUND: Pentoxifylline (PTX), a methylxanthine derivate with immunomodulating properties, has been used as adjunctive treatment in severe neonatal sepsis. The aim of the study was to investigate the anti-inflammatory effects of PTX on Lipopolysaccharides (LPS)-stimulated monocytes of pre term neonates in vitro compared with monocytes of term infants and adult controls. METHODS: Whole cord blood samples and control adult blood samples were incubated with LPS and PTX. The expression of surface markers, phagocytosis, cytokine secretion, and Toll-like receptor (TLR)4 signaling of monocytes were assessed by flow cytometry. Changes of TLR4-messenger RNA (mRNA) levels were confirmed by reverse-transcriptase PCR. RESULTS: The expression of CD14, CD11 b, CD64, CD71, and CD80 was downregulated by PTX in a dose -dependent manner; the greatest effect was observed on CD14 and CD11b in preterm infants. PTX markedly downregulated LPS-induced tumor necrosis factor-alpha, interleukin (IL)-1 beta, and IL-6 levels in all age groups. Early IL-10 production was significantly downregulated by PTX in term and preterm neonates, while remaining unchanged in adults. Moreover, PTX downregulated TLR4 expression of monocytes on cellular and mRNA level, decreased signaling, and suppressed phagocytosis. CONCLUSION: PTX downregulated TLR4 expression and signaling, thereby leading to strong anti-inflammatory properties in monocytes. Age -dependent differences were identified for CD14 and CD11 b expression and IL-10 production.