Serum tumour necrosis factor in newborns at risk for infections

Girardin, Éric; Berner, Michel; Grau, Georges E.; Suter, Susanne; G, Lacourt; Paunier, L

doi:10.1007/bf02034754

Cited by 69 publications

(38 citation statements)

References 13 publications

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“…Neopterin and soluble IL-2R levels have been shown to be positively correlated with active Crohn's disease [10], but there have been no previous studies on neopterin in neonates. TNF-is known to be an important mediator in the pathogenesis of Gram-negative shock [11] and, in experimental rats, it has been shown to be involved in the development of necrotizing enterocolitis (NEC) [12,13]. The production of TNFby preterm infants during infection has been documented [11], but, along with other cytokines (e. g. IFN-), it is readily taken up into cells [8].…”

Section: Introductionmentioning

confidence: 99%

“…TNF-is known to be an important mediator in the pathogenesis of Gram-negative shock [11] and, in experimental rats, it has been shown to be involved in the development of necrotizing enterocolitis (NEC) [12,13]. The production of TNFby preterm infants during infection has been documented [11], but, along with other cytokines (e. g. IFN-), it is readily taken up into cells [8]. It is possible that such molecules could be used as markers for detecting and monitoring bacterial sepsis and viral infections in the newborn.…”

Section: Introductionmentioning

confidence: 99%

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Inflammatory and immunological markers in preterm infants: correlation with disease

Jurges

Henderson

1996

Clinical and Experimental Immunology

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SUMMARYNewborn infants often suffer from bacterial and viral infections without presenting typical symptoms. Therefore, reliable methods for detecting and monitoring sepsis in the newborn would be beneficial. In older patients C-reactive protein (CRP) and neopterin have proved useful serum markers of infection and inflammation. Both of these markers are regulated by cytokines, and it has been proposed that cytokines themselves could be used to monitor immune activation and infection. This study has examined the levels of CRP, neopterin, soluble IL-2R, tumour necrosis factor-alpha (TNF-) and interferon-gamma (IFN-) in cord blood samples from both pre-mature and term neonates. Having established reference ranges for these analytes, serial measurements were made in babies requiring intensive care support. The results suggest that in preterm infants the simultaneous measurement of CRP and neopterin, and possibly soluble IL-2R, may provide an accurate early diagnosis of sepsis and may be of use in differentiating between bacterial and viral etiologies. In addition, serial measurement of these markers may help in the early diagnosis of necrotizing enterocolitis (NEC).

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Inflammatory and immunological markers in preterm infants: correlation with disease

Jurges

Henderson

1996

Clinical and Experimental Immunology

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“…TNF-␣ increases in the plasma during septic shock (12), and TNF-␣ injection induces hypotension, metabolic alteration, and death in animals (13). TNF-␣ injection into adult mice decreases gluconeogenesis, PEPCK gene expression, and plasma glucose concentration (14,15).…”

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confidence: 99%

TNFα Decreases Gluconeogenesis in Hepatocytes Isolated from 10-Day-Old Rats

et al. 2001

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Gluconeogenesis decreases during septic shock, but its mechanism is not well known. Tumor necrosis factor alpha (TNF-␣), which is a key cytokine in septic shock, can increase GLUT1 gene expression and glucose uptake in muscles and fatty tissues. TNF-␣ does not alter the metabolism of hepatocytes in which GLUT2 is the predominant glucose transporter. However, GLUT1 is the predominant glucose transporter in hepatocytes of 10-d-old rats. Thus, we hypothesized that TNF-␣ might increase glucose uptake and glycolysis in those cells, and decrease gluconeogenesis. In the present study, hepatocytes isolated from 10-d-old rats were incubated with TNF-␣ at the concentrations of 0, 0.98, 9.8, 98, and 980 ng/mL to evaluate TNF-␣ effects on gluconeogenesis and glucose uptake. TNF-␣ increased glucose uptake (41.1 Ϯ 8 to 114 Ϯ 21.4 mol/10 6 cells at the concentration of 980 ng/mL of TNF-␣) in a dose-dependent manner, and decreased gluconeogenesis (98.2 Ϯ 8.2 to 1.1 Ϯ 3.2 mol/10 6 cells at the concentration of 980 ng/mL of TNF-␣) in a dosedependent manner. The decrease of glucokinase mRNA and GLUT1 mRNA abundance correlated with glucose uptake (r ϭ 0.988 and 0.997, respectively), and the decrease of phosphoenolpyruvate carboxykinase mRNA abundance correlated with the decrease of gluconeogenesis (r ϭ 0.972). The decrease of gluconeogenesis by TNF-␣ correlated with the increase of glucose uptake (r ϭ Ϫ0.988). We concluded that TNF-␣ reciprocally suppressed gluconeogenesis in hepatocytes isolated from 10-dold rats. Gram-negative septic shock in the newborn remains a major medical problem because of its high incidence and mortality. Endotoxin (lipopolysaccharide: LPS), a component of outer cell membrane of Gram-negative bacteria, plays an important role in Gram-negative septic shock. Whereas the LD 90 of Salmonella enteritidis LPS is 0.1 mg/kg in 10-d-old rats, it is 35 mg/kg in adult rats (1), indicating that the newborn is more sensitive to LPS than the adult. The high sensitivity to LPS in the newborn is ascribed to immature pituitary-adrenal function (2), but this alone cannot fully explain the mechanism of the high sensitivity.Glucose dyshomeostasis such as hyperglycemia and hypoglycemia is a common sign in Gram-negative septic shock (1, 3-5). Because severe hypoglycemia may result in severe neurologic sequelae in the newborn, hypoglycemia during shock is a critical problem. During septic shock, glycolysis is increased and gluconeogenesis is decreased in the liver (4, 5). The activity and mRNA abundance of PEPCK, a key gluconeogenic enzyme, are decreased during septic shock (5-7). Because gluconeogenesis is necessary to maintain plasma glucose concentration in the newborn, even at the postprandial state (8), decrease of gluconeogenesis may easily lead to hypoglycemia. Because plasma concentration of insulin, which is a major glucoregulatory hormone and can inhibit gluconeogenesis, increases during septic shock in the adult (1, 3, 9), hyperinsulinemia is postulated to be responsible for the hypoglycemia in adults. In contrast to...

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“…Endotoxin or lipopolysaccharide (LPS)-produced by gram-negative organisms cause monocytes and macrophages [2] to produce several cytokines including TNF-· [3], which mediates organ dysfunction in sepsis. TNF-· has been linked to increased production of the inducible isoform of nitric oxide synthase (iNOS), increased generation of reactive oxygen species by vascular smooth muscle cells and direct negative nitropic effects on cardiac myocytes, apoptosis and ventricular remodeling, the latter as noted by increased production and accumulation of new collagen within the injured myocardium [4][5][6][7][8].…”

Section: Introductionmentioning

confidence: 99%

LPS-Induced Changes in Myocardial Markers in Neonatal Rats

Ravindranath

Gotō²,

Bakr³

et al. 2003

Neonatology

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Lipopolysaccharide (LPS) produces varied systemic metabolic effects. We studied the effects of LPS on the cardiac fatty acid profile and its relationship to energy metabolism and inflammatory mediators that included TNF-α and nitric oxide synthase (NOS) in 10-day-old neonatal rat pups. Rat pups received an i.p. injection of LPS after a 4-hour starvation period, followed by collection of blood and cardiac tissue 4 h following LPS administration. Compared to controls, LPS induced significant hypoglycemia and hyperlactacidemia, suggesting the development of endotoxic shock. The result was a significant depression in total fatty acid levels as well as non-esterified fatty acid in the cardiac tissue of the LPS-treated pups. In addition, LPS-treated pups also showed a significant increase in TNF-α, NOS levels with a depressed redox state and energy metabolism in cardiac tissue. These observations suggest that endotoxic shock in 10-day-old rat pups induces a systemic inflammatory response with a depression in fatty acid metabolism that may contribute to myocardial failure.

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Serum tumour necrosis factor in newborns at risk for infections

Cited by 69 publications

References 13 publications

Inflammatory and immunological markers in preterm infants: correlation with disease

Inflammatory and immunological markers in preterm infants: correlation with disease

TNFα Decreases Gluconeogenesis in Hepatocytes Isolated from 10-Day-Old Rats

LPS-Induced Changes in Myocardial Markers in Neonatal Rats

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