Neutrophil storage pool depletion in septic, neutropenic neonates

Jg, Wheeler; Ar, Chauvenet; Ca, Johnson; Dillard, Robert G.; Sm, Block; R, Boyle; Js, Abramson

doi:10.1097/00006454-198409000-00003

Cited by 39 publications

(11 citation statements)

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“…Despite this increased demand for neutrophils, the NSP (composed of 5-7 X lo9 segmented neutrophils, band neutrophils, and metamyelocytes per kg of body weight) rarely becomes completely depleted (1,13,15,16). In prematurely delivered neonates, however, complete depletion of the NSP is a relatively common sequelae of bacterial infection, frequently accompanied by profound neutropenia, overwhelming sepsis, and death (2,3,(17)(18)(19)(20)(21).…”

Section: Discussionmentioning

confidence: 99%

Neutrophil Pool Sizes and Granulocyte Colony-Stimulating Factor Production in Human Mid-Trimester Fetuses

et al. 1995

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We quantified neutrophils and neutrophil progenitors, and assessed granulocyte colony-stimulating factor (G-CSF) production in the liver and bone marrow of 20 human abortuses after elective pregnancy termination between 14 and 24 wk of gestation. Mature neutrophils were not observed in any of the liver specimens, but were present in the bone marrow as early as 14 wk. The concentrations of neutrophils in the fetal marrow were extremely low, by comparison with term infants and adults, with less than 5% of the nucleated cells being segmented neutrophils, band neutrophils, or metamyelocytes compared with 31-69% in term infants. Despite the low neutrophil populations, progenitors which had the capacity for clonal maturation into neutrophils in vitro were abundant in the fetal liver and fetal bone marrow. In addition, such progenitors had a dose-response relationship to recombinant G-CSF similar to that of progenitors from the bone marrow of healthy adults. At each gestational age tested, stimulation of mononuclear cells from fetal liver with IL-la generated less G-CSF protein and fewer G-CSF mRNA transcripts than did stimulation of mononuclear cells from fetal bone marrow. Mononuclear cells from the fetal bone marrow produced less G-CSF protein and mRNA than did mononuclear cells from the blood of The NSP is the sum of all segmented neutrophils, band neutrophils, and metamyelocytes held in reserve for ready release into the circulation (1). Rat pups delivered prematurely have a much smaller NSP, per g of body weight, than do those delivered at term, and pups delivered at term have a smaller NSP than do adult rats (2-6). It is unknown, however, whether this observation applies to humans. Studies employing cells

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Section: Discussionmentioning

confidence: 99%

Neutrophil Pool Sizes and Granulocyte Colony-Stimulating Factor Production in Human Mid-Trimester Fetuses

et al. 1995

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“…3,4 Mortality from neonatal sepsis depends upon the virulence of the organism, the gestational age of the neonate, and the particular combination and severity of the patient's concomitant illnesses. 1,[5][6][7] Neonatal sepsis is also commonly associated with neutropenia 8,9 as a result of a shortened neutrophil half-life from 6.3 hours to less than 4 hours, 10 a limited ability to augment production of the neutrophil proliferative pool, defective production of cytokines, and a rapid depletion of the infant's neutrophil storage pool during bacteremia. [11][12][13] The resulting neutropenia serves as an ominous marker for an exaggerated additional risk of mortality attributable to sepsis which rises to as high as 90%.…”

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confidence: 99%

Human Granulocyte Colony-stimulating Factor May Improve Outcome Attributable to Neonatal Sepsis Complicated by Neutropenia

Kocherlakota

Gamma

1997

Pediatrics

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ABSTRACT. Objectives. To determine whether adjunctive therapy with recombinant human granulocyte colony-stimulating factor (rhG-CSF) could reverse sepsis-associated neonatal neutropenia and improve neonatal survival compared with conventional therapy in a phase I/II-type trial.Study Design. An intravenous infusion of rhG-CSF (10 g/kg/d ؋ 3 d) was administered to 14 septic neutropenic neonates. Neutrophilic responses and outcome of these neonates were compared with 11 concurrently treated, retrospectively selected, case-matched control septic patients identified by using a search of medical records coded for sepsis with neutropenia ( 24 hours).Results. Seven neonates with early-onset sepsis with neutropenia at birth and seven neonates with late-onset sepsis plus neutropenia (all with necrotizing enterocolitis) were entered in the rhG-CSF treatment group. Results were compared with a conventional therapy control group (five early onset, six late onset). No significant differences existed in the birth weight, gestational age, use of antibiotic therapy, magnitude of respiratory support, severity of metabolic acidosis, use of vasopressors, or other supportive therapy between the two groups. In the rhG-CSF-treated group and in the conventionally treated control group, the absolute neutrophil count (ANC) (mean ؎ SEM) was 585 ؎ 138 and 438 ؎ 152, respectively. The ANC increased to more than baseline in the rhG-CSF-treated group by 10-fold versus 2-fold at 24 hours, 18-fold versus 4-fold at 48 hours, 24-fold versus 5-fold at 72 hours (significant by one-way analysis of variance in the rhG-CSF group only), and 29-fold versus 16-fold at 7 to 10 days when compared with the conventional therapy group. There were no nonresponders in the rhG-CSF group by 24 hours after the first dose of study drug. Monocyte cell counts also increased significantly in both groups by 7 days after entry into this protocol but remained within normal range for age. No clinically significant effect on lymphocytes, erythrocytes, or platelet counts was noted. Thirteen patients in the rhG-CSF-treated group (92%; 13 out of 14) and five in the conventionally treated group (55%; 5 out of 11) survived to 28 days after the onset of the signs of sepsis. No adverse effects were noted in the rhG-CSF-treated group.Conclusions. rhG-CSF can increase the neutrophil count in critically ill septic neutropenic neonates. This finding suggests that rhG-CSF may be effective in a therapeutically useful time frame to treat septic neonates with neonatal neutropenia attributable to bone marrow suppression or neutrophil consumption. Future randomized trials are needed to validate the beneficial effects of rhG-CSF and to determine whether any significant side effects of therapy exist. Pediatrics 1997;100(1). URL: http: //www.pediatrics.org/cgi/content/full/100/1/e6; neonatal sepsis, recombinant human granulocyte colony stimulating factor, bacteremia, cytokines, very low birth weight, neutropenia.

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“…They, however, have a short life span, about 6 h, and rapidly undergo apoptosis in blood circulation (1). Granulocytopenia is a poor prognostic factor for patients in neonatal intensive care units (2). It is known that the counter-regulation between apoptotic and anti-apoptotic signals determines the death program of granulocytes (3,4).…”

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Higher Spontaneous and TNFα-Induced Apoptosis of Neonatal Blood Granulocytes

Liu

Wang

et al. 2005

Pediatr Res

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Granulocytes play an important role in inflammatory diseases. Neonates tend to develop granulocytopenia under sepsis and stress. It remains unclear whether apoptosis of neonatal granulocytes is different from that of adult granulocytes. In this study, we analyzed the discrepancy of granulocyte apoptosis between cord blood (CB) and adult blood (AB). We found that spontaneous and tumor necrosis factor-␣ (TNF␣)-induced granulocyte apoptosis as determined by phosphatidylserine expression and DNA fragmentation were more prominent in CB granulocytes than AB granulocytes. CD95 ligand and TNF␣ levels were significantly higher in CB than in AB (p ϭ 0.001 and p Ͻ 0.001, respectively). TNF receptor-2 and CD95 expression on CB granulocytes were not different from those on AB granulocytes. However, the TNF receptor-1 (TNFR1) expression was lower on CB granulocytes than that on AB granulocytes (69.98 Ϯ 7.32 versus 89.04 Ϯ 3.73%, p ϭ 0.029). This decrease of TNFR1 expression on neonatal granulocytes might be related to a higher plasma TNF␣ level associated with an intrinsic defect on the dynamic change of membrane TNFR1 expression in neonatal granulocytes. The expression of anti-apoptotic molecule Bcl-2 in neonatal granulocytes was also lower than that in adult granulocytes (4.64 Ϯ 0.51 versus 7.24 Ϯ 1.17 unit/mg protein, p ϭ 0.032). Moreover, another anti-apoptotic signal, nuclear factor-B nuclear translocation, was also lower in CB than AB granulocytes. Results from this study suggest that higher plasma death ligands associated with lower anti-apoptotic molecules in granulocytes may act an important role in triggering neonatal granulocyte apoptosis. Granulocytes play an important role in inflammatory diseases and provide a first-line defense against bacterial infections. They, however, have a short life span, about 6 h, and rapidly undergo apoptosis in blood circulation (1). Granulocytopenia is a poor prognostic factor for patients in neonatal intensive care units (2). It is known that the counter-regulation between apoptotic and anti-apoptotic signals determines the death program of granulocytes (3,4). It is not known whether abnormal plasma death ligands or intracellular anti-apoptotic molecules are involved in the susceptibility of granulocyte apoptosis in neonates.Newborns tend to develop granulocytopenia in overwhelming infections or stress. Certain studies have indicated that neonatal leukocytes are functionally immature and have deficient immune responses compared with adult ones (5,6). However, some studies demonstrated that the immune responses of newborns are similar to those of adults but are diminished under stress (7). It remains unclear whether susceptibility to granulocytopenia in neonates is related to faster cell program death (apoptosis) or to stress-induced alteration and consumption. Allgaier et al. (8) reported that neonatal granulocytes underwent apoptosis slower than adult ones. In contrast, Uguz et al. (9) found that granulocytes from neonates underwent faster apoptosis than adult granulocytes. The...

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Neutrophil storage pool depletion in septic, neutropenic neonates

Cited by 39 publications

References 0 publications

Neutrophil Pool Sizes and Granulocyte Colony-Stimulating Factor Production in Human Mid-Trimester Fetuses

Neutrophil Pool Sizes and Granulocyte Colony-Stimulating Factor Production in Human Mid-Trimester Fetuses

Human Granulocyte Colony-stimulating Factor May Improve Outcome Attributable to Neonatal Sepsis Complicated by Neutropenia

Higher Spontaneous and TNFα-Induced Apoptosis of Neonatal Blood Granulocytes

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