CD14 Receptor Expression and Lipopolysaccharide-Induced Cytokine Production in Preterm and Term Neonates

Bessler, Hanna; Komlos, L.; Punsky, Igor; Ntambi, J.A.; Bergman, Michael; Straussberg, R; Sirota, Lea

doi:10.1159/000047141

Cited by 24 publications

(15 citation statements)

References 25 publications

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“…TNF-a was measured by ELISA (n=5). Data representative of mean ± SD of the innate immune system to mount an effective response allowing rapid progression to multiple organ dysfunction [29].The data presented here agrees with the published literature demonstrating that neonatal monocytes produce equivalent levels of IL-6, IL-8 and IL1-b, with TNF-a the only element of the pro-inflammatory response to exhibit reduced levels following LPS and Pam-3-Cys stimulation [30][31][32][33]. The results also show that IL-10 production is significantly reduced in relation to adult monocytes following stimulation with LPS, Pam-3-Cys and TNF-a.…”

Section: Discussionsupporting

confidence: 86%

TNF-α is a mediator of the anti-inflammatory response in a human neonatal model of the non-septic shock syndrome

2005

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The anti-inflammatory/immunoparalytic phase of the systemic inflammatory response syndrome (SIRS) following major insult (surgery, thermal/traumatic injury) is of major clinical importance in the neonate, during which the risk of infection is particularly great. Here, the mechanisms by which TNF-a production is suppressed in response to infection are largely unknown. We questioned whether TNF-a itself could be a critical mediator of this suppression. Monocytes, isolated from cord blood (n=3), were treated with LPS (100 ng/ml), TNF-a (10 ng/ml, +/À anti-TNF-a antibody) for 18 and 36 h. Cells were then restimulated with LPS (Gram Àve) or Pam-3-Cys (Gram +ve) for 24 h. This was also done in the presence of selective inhibitors of MAP kinases p38, MEK and JNK. TNF-a, IL-6, IL-10 and IL-8 were quantified by ELISA CD86 and HLA-DR expression were determined flow cytometrically. Cells stimulated with LPS for 24 h produced TNF-a (282 pg/ ml), IL-10 (1,236 pg/ml), IL-6 (2,694 pg/ml) and IL-8 (2,144 pg/ml). In cells pre-exposed to TNF-a for 36 h, there was a significant suppression in TNF-a and IL-6 levels (9 and 221 pg/ml, respectively) (P<0.05) with minimal impact on IL-10 (1,206 pg/ml) and IL-8 levels (1,886 pg/ml). A similar effect was seen with Pam-3-Cys with a tenfold decrease in levels of TNF-a and IL-6 (86 fi 8.5 pg/ml and 458 fi 46 pg/ml, respectively) with no effect on IL-10 and IL-8 levels. Anti-TNF-a antibody negated this effect. Inhibition of p38 kinase reversed the TNF-a effect. Inhibition of the JNK and MEK kinases had no effect. A reduction in the expression of CD86 and HLA-DR was observed. This ex-vivo model of non-septic SIRS demonstrates that TNF-a, released during a major insult, can suppress subsequent monocyte responses to bacterial agents through p38 MAP kinase, making it a potential therapeutic target.

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Section: Discussionsupporting

confidence: 86%

TNF-α is a mediator of the anti-inflammatory response in a human neonatal model of the non-septic shock syndrome

2005

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“…Previous studies have shown that the basal cytokine release from blood cells is lower in children than adults, which is consistent with our data (16,17). The capacity of the infant cells to respond to E. coli culture supernatant was well developed.…”

Section: Laestadius Et Alsupporting

confidence: 93%

Developmental Aspects of Escherichia coli–Induced Innate Responses in Rat Renal Epithelial Cells

et al. 2003

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“…Clinical (8)(9)(10)(11)(12) and animal studies (13)(14)(15) indeed have shown reduced expression of TLR2 and TLR4, as well as diminished function in cytokine production induced by their agonists at birth, in preterm newborns. However, deficiencies in the TLR system at birth do not necessarily mean that it does not improve during the early postnatal period.…”

mentioning

confidence: 99%

Development of monocyte Toll-like receptor 2 and Toll-like receptor 4 in preterm newborns during the first few months of life

et al. 2013

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Background: Although the immaturity of Toll-like receptor 2 (TLR2) and Toll-like receptor 4 (TLR4) at birth in preterm newborns is known, their development during the first few months of life remains unclear. Methods: Blood monocytes of preterm newborns (gestational age: 24-36 wk) were obtained every 2 wk when possible in order to perform serial measurements of TLR2 and TLR4 surface expression, as well as lipopolysaccharide (LPS)-induced cytokine production. Measurements using monocytes from term newborns and adults were also performed. results: The monocytes of preterm newborns obtained at birth displayed reduced surface expression of TLR2 and TLR4, and diminished responses of tumor necrosis factor-α (TNF-α) and interleukin (IL)-8 to LPS stimulation. Regardless of gestational age, monocyte expression of TLR2 and TLR4 in preterm newborns increased rapidly within the first 2 wk after birth, quickly reaching those of term newborns. These increases continued for the following 4-6 wk, although the increase began to plateau. By contrast, LPS-induced production of TNF-α and IL-8 did not elevate over this period in preterm newborns. conclusion: The blood monocytes of preterm newborns display rapid increase in TLR2 and TLR4 expression during the first few months of life, whereas LPS-induced cytokine production functionality did not improve in parallel.

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CD14 Receptor Expression and Lipopolysaccharide-Induced Cytokine Production in Preterm and Term Neonates

Cited by 24 publications

References 25 publications

TNF-α is a mediator of the anti-inflammatory response in a human neonatal model of the non-septic shock syndrome

TNF-α is a mediator of the anti-inflammatory response in a human neonatal model of the non-septic shock syndrome

Developmental Aspects of Escherichia coli–Induced Innate Responses in Rat Renal Epithelial Cells

Development of monocyte Toll-like receptor 2 and Toll-like receptor 4 in preterm newborns during the first few months of life

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