Neonatal Tumor Necrosis Factor, Interleukin-1α, Interleukin-1β, and Interleukin-6 Response to Infection

Özdemir, Ali; Oygür, Nihal; Gültekin, Meral; Çoşkun, Mesut; Yegin, Olcay

doi:10.1055/s-2007-994592

Cited by 45 publications

(42 citation statements)

References 3 publications

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“…However, the proportion of T cells in peripheral blood is lower, especially in infants who are small for gestational age [51][52][53]. Clinical evidence has shown that extremely high levels of cytokines can be detected in certain infant diseases linked to mild infections [54][55][56][57][58]. Therefore, a lack of T cells would increase the risk of excessive innate activation and consequent immunopathology, higher morbidity and mortality in response to infection.…”

Section: Discussionmentioning

confidence: 99%

A new role for T cells in dampening innate inflammatory responses

Tang

2010

Sci. China Life Sci.

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Section: Discussionmentioning

confidence: 99%

A new role for T cells in dampening innate inflammatory responses

Tang

2010

Sci. China Life Sci.

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“…There is also evidence in the literature that the persistence of TNF-␣ rather than peak levels predicts poor outcome in patients with sepsis and septic shock [17][18][19], therefore a genetic marker for high and long-lasting secretion might be more predictive.Although high TNF-␣ plasma concentrations have been correlated with a severe clinical course and poor outcome in neonatal sepsis [9][10][11], others could not find any difference in serum TNF-␣ levels in preterm and full-term infants neither in septic nor control groups [20]. Ozdemir et al did not find a statistically significant correlation between TNF-␣, interleukin (IL)-1␤, IL-6, CRP, leukocyte and thrombocyte counts and the outcome in neonatal sepsis [21]. One study even demonstrated a protective role of this cytokine, as its detection was predictive of good outcome in adult septic patients [22] or presented evidence that patients with low production of TNF-␣ were at risk for fulminant meningococcal disease [8].As stated in the literature, TNFB2 homozygous individuals had increased circulating TNF-␣ plasma concentrations in vitro [15,16] and in vivo [14].…”

Section: Discussionmentioning

confidence: 99%

Pilot Study Assessing TNF Gene Polymorphism as a Prognostic Marker for Disease Progression in Neonates with Sepsis

2000

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In adult postoperative intensive care patients, the biallelic Ncol polymorphism within the tumor necrosis factor (TNF) locus has been shown to be a genomic marker for individuals with increased TNF-alpha response and poor prognosis in severe sepsis. We characterized the genomic distribution and allele frequency of the Ncol polymorphism in 23 preterm and term neonatal intensive care unit (NICU) patients with culture-proven sepsis and compared it with clinical and laboratory characteristics to assess its prognostic value for disease progression. Genotype analysis demonstrated the following absolute (relative) frequencies: 7 (0.31) infants were homozygous for the allele TNFB2 (Group A). 12 (0.52) infants were heterozygous (TNFB1/TNFB2) and four (0.17) infants homozygous for the allele TNFB1 (Group B). There was no significant difference compared to adult intensive care patients with severe sepsis (p = 0.31). The median gestational age of all infants (13 female and ten male) as well as for either group was 28 weeks (range 23-37) with a median birth weight of 845 g (range 560-2,720). The study population included a total of 16 very low birth weight (VLBW) infants, four in Group A and 12 in Group B. However, there was no significant difference for gestational age and birth weight in both groups (p = 0.82 and 0.71, respectively). Laboratory parameters as maximum and minimum leukocyte and thrombocyte counts, maximum immature to total neutrophil ratios (ITR), maximum C-reactive protein (CRP) levels, days of CRP levels > 5 mg/l and total days of antibiotic treatment, were not statistically different in both groups. In total, three infants (13%) died in consequence of their underlying disease. Two infants belonged to Group A and one to Group B. The statistical analysis of outcome variables (mortality, neurological impairment, failure to thrive) was not possible, because the study population was small and the reasons for poor outcome and death in these high-risk patients had to be considered multifactorial. In conclusion, in this pilot study the biallelic Ncol polymorphism within the TNF locus was not a prognostic marker for disease progression in high-risk NICU-admitted term and preterm infants with culture-proven sepsis. In order to detect differences in outcome similar to adult postsurgical patients with severe sepsis, an unfeasibly high number of NICU patients with culture-proven sepsis would need to be included for a similar study.

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“…Extensive clinical evidence already suggests that excessive cytokines in newborns might contribute to mortality and morbidity in postnatal infection. In neonatal sepsis, overwhelming amounts of TNF and IL-6 are detected in serum (39,40). Necrotizing enterocolitis, an intestinal disease that occurs frequently in preterm newborns, is thought to be due to a robust intestinal epithelial inflammatory responses to bacterial infection (9).…”

Section: 01) Data Are Presented As Mean Values (ϯSem) (D) Lethal mentioning

confidence: 99%

Hyper innate responses in neonates lead to increased morbidity and mortality after infection

Zhao

Kim

Yang

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

144

128

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Neonates suffer high morbidity and mortality in infection, presumably because of the lack of a fully developed adaptive and innate immune system. Evidence of poor innate responses in neonates has been shown by using a model that sensitizes the host to Toll-like receptor (TLR)-mediated inflammation with D-galactosamine (DGalN). However, we show that neonatal mice demonstrate much stronger inflammatory responses than adult mice in response to LPS stimulation, and such hypersensitivity extends to other TLR agonists including actual viral infection. Our study reveals that the ensuing inflammatory reaction after D-GalN sensitization reflects preferential toxicity of D-GalN to adult liver cells, rather than accurately reflecting the TLR response to LPS. We show further that an uncontrolled proinflammatory innate response due to inadequate T cells makes neonates more vulnerable to TLR agonists or viral infection. Remarkably, through transfer of T cells into neonates or depletion of T cells in adult mice, we show that T cells are sufficient and necessary to control the early inflammatory response to LPS. Therefore, neonates might suffer from the unleashed innate responses caused by an insufficient number of T cells, which leads to increased morbidity and mortality.

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Neonatal Tumor Necrosis Factor, Interleukin-1α, Interleukin-1β, and Interleukin-6 Response to Infection

Cited by 45 publications

References 3 publications

A new role for T cells in dampening innate inflammatory responses

A new role for T cells in dampening innate inflammatory responses

Pilot Study Assessing TNF Gene Polymorphism as a Prognostic Marker for Disease Progression in Neonates with Sepsis

Hyper innate responses in neonates lead to increased morbidity and mortality after infection

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