Il-1β, Il-6, Il-8 and G-CSF in the diagnosis of early-onset neonatal infections

Büscher, Ulrich; Chen, Frank C.-K.; Pitzen, Alois; Menon, Ramkumar; Vogel, Martin; Obladen, Michael; Dudenhausen, Joachim W.

doi:10.1515/jpm.2000.049

Cited by 29 publications

(16 citation statements)

References 25 publications

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“…Several other studies have shown that neonatal sepsis is associated with increases in plasma cytokine levels such as IL-6, IL-8 and TNFa , G-CSF, IFNg , IL-1ra and IL-1 b [1,2,4]. We have now shown that neonatal sepsis is associated with significantly increased levels of IL-10, IL-12 and IL-6 in newborns aged 1-7 days and increased levels of IL-10 and IL-12 in neonates aged 15-21 days.…”

Section: Discussionmentioning

confidence: 94%

Rapid simultaneous measurement of multiple cytokines using 100 µl sample volumes − association with neonatal sepsis

Hodge

Haslam³

et al. 2004

Clinical and Experimental Immunology

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SUMMARYEarly diagnosis of neonatal infection has proved problematic due to the inadequacy of currently available laboratory tests. Neonatal sepsis is associated with an increase in plasma-derived cytokine levels, but an increase of a single cytokine cannot identify neonatal sepsis specifically and multiple cytokine levels are required. The time constraints and relatively large volume of plasma required to measure multiple cytokines from newborn infants by conventional enzyme-linked immunosorbent assay (ELISA) techniques is prohibitive. We therefore applied cytometric bead array (CBA) technology for simultaneous measurement of multiple cytokines from a group of 18 term neonates with infection confirmed by culture and a control group. 'Normal' ranges were established for each cytokine from 1-7-, 8-14-and 15-21-day-old newborns. There was no significant change in the levels of cytokines from infants in different control age groups, suggesting that basal cytokine levels are unchanged in the first 3 weeks of life. In the patient groups, however, there was a significant difference in several cytokines between the different age groups. Interleukin (IL)-6, IL-10 and IL-12 were increased significantly in the 1-7-day-old patient group compared to either the 8-14 and 15-21 age group, suggesting that infection in utero is associated with increased levels of these cytokines compared to infection acquired following birth. When individual patient cytokine levels were compared to normal control reference ranges, two patients failed to show significant elevation of any cytokine tested. All other patients showed elevated levels of between one and nine cytokines tested (mean of 4·6). There was no correlation between elevated cytokine levels and types of infective organism or patient age. In conclusion, neonatal sepsis is associated with the elevation of multiple plasma cytokines. The use of CBA kits is a rapid, easy, low sample volume and sensitive method to measure multiple plasma cytokines.Keywords cytokines cytometric bead array flow cytometry inflammatory neonatal sepsis Th1/ Th2

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Section: Discussionmentioning

confidence: 94%

Rapid simultaneous measurement of multiple cytokines using 100 µl sample volumes − association with neonatal sepsis

Hodge

Haslam³

et al. 2004

Clinical and Experimental Immunology

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“…Some of our findings of cytokine levels measured in TA fluid are in agreement with previous studies on cytokine levels in umbilical cord blood in neonates with HC. Indeed, higher IL-6 blood levels and IL-1␤ were found in neonates in whom HC was present (17)(18)(19). Elevated cord blood IL-6 concentrations were associated with decreased blood pressure in premature newborns and therefore may predispose such infants to perinatal brain injury (19).…”

mentioning

confidence: 99%

Relationship between Histologic Chorioamnionitis and Early Inflammatory Variables in Blood, Tracheal Aspirates, and Endotracheal Colonization in Preterm Infants

et al. 2003

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Histologic results of the placenta are usually not available within the first days of life. We identified inflammatory variables in tracheal aspirates and blood that were associated with histologic chorioamnionitis (HC). A derivation cohort consisted of 62 neonates and a validation cohort of 57 neonates with a gestational age Ͻ 31 wk and ventilated on d 1. Tracheal aspirates were taken on d 1 and on d 3, if the patient was still ventilated. HC was diagnosed by light microscopy. Logistic regression was used to identify independent factors in the derivation cohort associated with HC at d 1, 2, and 3. Model performance was studied using receiver operating characteristic curve analysis. Independent factors associated with HC were, at d 1, tracheal aspirate IL-8 Ն 917 pg/mL (odds ratio, 60.7; 95% confidence interval, 11-328); at d 2, blood C-reactive protein Ն 14 mg/L (odds ratio, 9.2; 95% confidence interval, 2-38), blood white blood cell count Ն 10,400/mm 3 (odds ratio, 7.4; 95% confidence interval, 2-28); and at d 3, blood neutrophil count Ն 4968/mm Chorioamnionitis is considered to be one of the main causes of preterm labor and has been associated with an adverse perinatal outcome (e.g. cerebral palsy and chronic lung disease) in preterm infants (1, 2). Histologic results of the examination of the placenta are usually not available within the first days of life, and prenatal diagnosis of chorioamnionitis remains difficult. An early diagnosis is difficult and can only be made in 6% to 24% of these patients by amniotic fluid culture (3). As a result of the "chronic inflammation" of fetal or maternal membranes, elevated proinflammatory cytokine levels are found in the amniotic fluid and ultimately in the fetus. These cytokines are associated with preterm labor and delivery, a fetal inflammatory response, and the associated negative outcomes (4, 5).The objective of the present study was to identify variables in the TA and blood of preterm infants, measured within the first 3 d of life, that are associated with HC in the placenta. These factors would allow us to identify infants with the highest risk of suffering from the adverse consequences of chorioamnionitis. METHODS Study population.

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“…Externally induced WBH induce production of the cytokines IL-1 and IL-6 in rats (41.5°C for 60 min) (16) and IL-1␤ and IL-6 in humans (41.8°C for 60 min) (17). Infection in normalweight and low-birth weight neonates may be predicted by increased levels of IL-6, and to a lesser extent IL-1␤ (18,19). Tobacco smoke, another important SIDS risk factor, may also influence cytokine production.…”

mentioning

confidence: 99%

Effects of Hyperthermia and Muramyl Dipeptide on IL-1β, IL-6, and Mortality in a Neonatal Rat Model

Nelson

Wong

et al. 2002

Pediatr Res

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The mechanism of sudden infant death syndrome (SIDS) may be linked to an interaction between the SIDS risk factors of hyperthermia and infection, and between their effect on cytokine production and arousal. This study investigated the effects of hyperthermia and a surrogate of infection (muramyl dipeptide or MDP) on cytokine production and mortality in a neonatal rat model. Four temperature groups were studied: 34°C (baseline), 38°C, 39°C, and 40°C. Body temperatures of neonatal rat pups in the hyperthermic groups were raised and maintained at the desired temperature (38°C, 39°C, or 40°C) for 1 h and then returned to the baseline temperature (34°C) for a further hour. The heat source was a covered, heatable aluminum metal plate in a Perspex heating chamber. Intraperitoneal (IP) injection of 0.1 mL normal saline was given 30 min before the start to control for MDP (protocol A). Four equivalent treatment groups were pretreated with MDP (25 nmol/animal) instead of normal saline (protocol B). IP ketamine (55 mg/kg) was used for anesthesia during the experiments and for euthanasia. Blood was collected by direct cardiac puncture immediately after the 2-h experiments and assayed for the cytokines IL-6 and IL-1␤ by ELISA. Hyperthermia significantly increased the production of IL-6 (p ϭ 0.049) but not IL-1␤ and significantly increased mortality. Administration of MDP significantly increased the IL-1␤ production (p ϭ 0.006) but not IL-6. Cox regression analysis showed that MDP in combination with hyperthermia had a significant effect on mortality in the neonatal rat. The risk of experiencing mortality was two and half times higher in the MDP group than in the non-MDP group (p ϭ 0.016) [hazard ratio (95% confidence interval) ϭ 2.66 (1.20 -5.92)]. We conclude that hyperthermia and a surrogate of infection (MDP) influence cytokine production and that the combination of heat stress and MDP increases mortality in the neonatal rat. Despite impressive recent decreases in incidence, SIDS remains a leading cause of postneonatal mortality in Western countries. These decreases in incidence have been attributed to campaigns advising parents and healthcare providers about modifiable SIDS risk factors. These factors, identified in numerous case-controlled studies, include prone (front) sleep position, smoking by mother or father, bed sharing (especially if the mother smokes), sleeping under bedclothes, not breastfeeding, and not using a pacifier (dummy) (1-4). Other factors such as young maternal age, low socioeconomic status, high parity, low birth weight, male infant, winter months, and cold climates have long been known to be associated with SIDS (5), but are to a large extent considered to be immutable or nonmodifiable. The prone sleep position is the most important SIDS risk factor and is likely to be causal (6). However, the mechanism whereby prone sleep position causes SIDS remains unknown. Suggested mechanisms include reduction of heat loss, which increases the risk of relative or absolute hyperthermia (7), rebreathing of expir...

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Il-1β, Il-6, Il-8 and G-CSF in the diagnosis of early-onset neonatal infections

Abstract: Il-6 in umbilical cord blood seems to be a promising predictor for early-onset neonatal infections.

Cited by 29 publications

References 25 publications

Rapid simultaneous measurement of multiple cytokines using 100 µl sample volumes − association with neonatal sepsis

Rapid simultaneous measurement of multiple cytokines using 100 µl sample volumes − association with neonatal sepsis

Relationship between Histologic Chorioamnionitis and Early Inflammatory Variables in Blood, Tracheal Aspirates, and Endotracheal Colonization in Preterm Infants

Effects of Hyperthermia and Muramyl Dipeptide on IL-1β, IL-6, and Mortality in a Neonatal Rat Model

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