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

Simone S. Schuller; Lukas Wisgrill; Elisabeth Herndl; Andreas Spittler; Elisabeth Forster-Waldl; Kambis Sadeghi; Boris W. Kramer; Angelika Berger

doi:10.1038/pr.2017.41

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

Simone S. Schuller, Lukas Wisgrill, Elisabeth Herndl, Andreas Spittler, Elisabeth Forster-Waldl, Kambis Sadeghi, Boris W. Kramer, Angelika Berger^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

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.

Original language	English
Pages (from-to)	215-225
Number of pages	11
Journal	Pediatric Research
Volume	82
Issue number	2
DOIs	https://doi.org/10.1038/pr.2017.41
Publication status	Published - Aug 2017

Keywords

PHOSPHODIESTERASE INHIBITOR
TNF-ALPHA
SEPSIS
EXPRESSION
INTERLEUKIN-10
PHAGOCYTOSIS
ENDOTOXEMIA
ACTIVATION
RECEPTORS
NEWBORN

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10.1038/pr.2017.41

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@article{86a52f6eecf1439bb188b31ef329c02a,

title = "Pentoxifylline modulates LPS-induced hyperinflammation in monocytes of preterm infants in vitro",

abstract = "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.",

keywords = "PHOSPHODIESTERASE INHIBITOR, TNF-ALPHA, SEPSIS, EXPRESSION, INTERLEUKIN-10, PHAGOCYTOSIS, ENDOTOXEMIA, ACTIVATION, RECEPTORS, NEWBORN",

author = "Schuller, {Simone S.} and Lukas Wisgrill and Elisabeth Herndl and Andreas Spittler and Elisabeth Forster-Waldl and Kambis Sadeghi and Kramer, {Boris W.} and Angelika Berger",

year = "2017",

month = aug,

doi = "10.1038/pr.2017.41",

language = "English",

volume = "82",

pages = "215--225",

journal = "Pediatric Research",

issn = "0031-3998",

publisher = "Nature Publishing Group",

number = "2",

}

TY - JOUR

T1 - Pentoxifylline modulates LPS-induced hyperinflammation in monocytes of preterm infants in vitro

AU - Schuller, Simone S.

AU - Wisgrill, Lukas

AU - Herndl, Elisabeth

AU - Spittler, Andreas

AU - Forster-Waldl, Elisabeth

AU - Sadeghi, Kambis

AU - Kramer, Boris W.

AU - Berger, Angelika

PY - 2017/8

Y1 - 2017/8

N2 - 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.

AB - 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.

KW - PHOSPHODIESTERASE INHIBITOR

KW - TNF-ALPHA

KW - SEPSIS

KW - EXPRESSION

KW - INTERLEUKIN-10

KW - PHAGOCYTOSIS

KW - ENDOTOXEMIA

KW - ACTIVATION

KW - RECEPTORS

KW - NEWBORN

U2 - 10.1038/pr.2017.41

DO - 10.1038/pr.2017.41

M3 - Article

C2 - 28288151

SN - 0031-3998

VL - 82

SP - 215

EP - 225

JO - Pediatric Research

JF - Pediatric Research

IS - 2

ER -