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Biomedical subjects

R D Christensen

Publications and source records attributed to R D Christensen.

At least 73 records · Page 4Linked to original sources
PubMed1996

Incidence, significance, and kinetic mechanism responsible for leukemoid reactions in patients in the neonatal intensive care unit: a prospective evaluation.

OBJECTIVE: To prospectively investigate the incidence, significance, and kinetic mechanism responsible for leukemoid reactions in patients in the neonatal intensive care unit (NICU). DESIGN: We prospectively studied all infants admitted to the NICU at the University of Florida who, during a period of 12 consecutive months, had a leukemoid reaction. All those identified had a standardized evaluation consisting of (1) karyotype analysis, (2) bacterial cultures, (3) evaluations for toxoplasmosis, other (congenital syphilis and viruses), rubella, cytomegalovirus, and herpes simplex virus) (TORCH), (4) determination of blood viscosity, (5) use of marrow aspirates for morphology, clonogenic progenitor cell assays, and cell-cycle analysis of progenitors, (6) determination of serum concentrations of granulocyte and granulocyte-macrophage colony-stimulating factors, and (7) serial complete blood cell counts until the leukemoid reaction remitted. RESULTS: During 12 months, 707 patients were admitted to the NICU and 4262 complete blood cell counts were performed on samples from these patients. A leukemoid reaction was identified in nine patients, all of whom were preterm (born at 24 to 38 weeks' gestation). Peak blood leukocyte concentrations were 51.7 +/- 15.6 x 10(3)/microl (mean +/- SD). The leukemoid reactions were detected during the first 4 days of life in seven patients, on day 9 in one, and on day 25 in one. An abnormal karyotype (47, XY, +21) was present in one infant. Mothers of four infants had received betamethasone antenatally. None had elevated whole blood viscosity or positive findings on bacterial or TORCH evaluations. None of the bone marrow findings were consistent with steroid-induced leukocytosis; all studies indicated accelerated neutrophil production. Serum concentrations of granulocyte-macrophage colony-stimulating factor were either negligible or nondetectable. Serum granulocyte colony-stimulating factor was elevated in three patients, low in two, and nondetectable in four. The leukemoid reactions persisted for 5 to 32 days, the longest being in the patient with trisomy 21. CONCLUSIONS: Leukemoid reactions were not particularly rare in our NICU (1.3% of patients). The reactions were not associated with hyperviscosity and, except in one patient with a karyotype abnormality, were transient. The responsible kinetic mechanism was increased neutrophil production, not steroid-induced leukocytosis.

Blood Viscosity↗
PubMed1996

Pharmacokinetics and effectiveness of recombinant erythropoietin administered to preterm infants by continuous infusion in total parenteral nutrition solution.

OBJECTIVES: To compare the pharmacokinetics and effectiveness of continuously administered recombinant erythropoietin (Epo) in total parenteral nutrition (TPN) solution with daily subcutaneously administered Epo. METHODS: Forty preterm infants in the first 72 hours of life were randomly assigned to receive Epo (200 units/kg per day for 10 consecutive days), either subcutaneously (20 infants, 1051 +/- 40 gm, 28.3 +/- 0.4 weeks of gestation; mean +/- SEM), or added daily to their TPN fluids (20 infants, 1028 +/- 36 gm, 27.9 +/- 0.4 weeks of gestation). Both groups received iron supplementation (1 mg/kg per day iron dextran in the TPN solution). Absolute reticulocyte counts and complete blood cell counts with differentials were measured, and transfusions and phlebotomy losses were recorded. Pharmacokinetics were determined in the first 16 infants. RESULTS: In the infants who received Epo subcutaneously, the elimination half-life was 17.6 +/- 4.4 hours on day 3 and 11.2 +/- 1.5 hours on day 10; the volume of distribution was 802 +/- 190 ml/kg on day 3 and 1330 +/- 243 m/kg on day 10. Serum Epo concentrations were higher on day 3 than on day 10 for both groups (subcutaneous: 400 +/- 64 mU/ml vs 177 +/- 29 mU/m, p <0.05; TPN: 395 +/- 64 vs 194 +/- 41 mU/ml, p <0.05). Clearance did not differ between the two groups with regard to route of administration and increased significantly from days 3 to 10 in both groups. Reticulocyte counts were similar in both groups. There were no differences between groups in the number of transfusions given, and the overall decline in hematocrit was similar. No adverse effects of Epo were noted in either group. CONCLUSIONS: Adding Epo to the TPN solution in this population results in similar Epo concentrations, clearance, and effectiveness as subcutaneous dosing.

Erythropoietin↗
PubMed1996

Production of granulocyte colony-stimulating factor by the human placenta at various stages of development.

The human placenta is capable of producing a variety of haematopoietic growth factors in vitro. It is not clear, however, whether the placenta produces such factors in vivo and if so, whether placental production of haematopoietic growth factors has a physiological role in fetal haematopoietic development. As a step toward making this determination, we assessed whether the onset of placental production of granulocyte colony-stimulating factor (G-CSF), in vivo, coincides with the onset of granulocytopoiesis in the developing fetus. To make this assessment, we obtained human placentae between 10 weeks of gestation and term and studied production of G-CSF in several ways. First, we sought to determine whether the onset of production of G-CSF mRNA in the placenta immediately precedes the appearance of neutrophil development in the fetus. Second, we assessed the effect of gestational age on the capacity of the placenta to generate G-CSF in vitro, by incubating cubes of placenta, with or without including interleukin-1 alpha (IL-1 alpha) in the culture media, and quantifying G-CSF in the cell culture supernatants 24 h later. Third, we assessed the rate of G-CSF production by the placenta, by perfusing two normal, term placentae using a membrane-oxygenator system, and quantifying G-CSF, at intervals, in the perfusates. We found: (1) no evidence that placental production of G-CSF is involved in regulating granulocytopoiesis in the fetus, (2) that the healthy placenta contains little or no G-CSF mRNA in vivo, (3) the placenta at term has a far greater capacity to produce G-CSF, when stimulated, than does the placenta before term, and (4) that although the placenta does not normally produce G-CSF in vivo, it has the capacity of generating very large quantities of G-CSF continuously over at least several days.

Blotting, Northern↗
PubMed1996

Effects of perinatal zidovudine on hematopoiesis: a comparison of effects on progenitors from human fetuses versus mothers.

OBJECTIVE: To compare the effects of zidovudine (ZDV) on clonal maturation of hematopoietic progenitors obtained from the bone marrow of women of child-bearing age with its effects on progenitors obtained from the marrow, liver and blood of fetuses. We also sought to determine whether the adverse effects of ZDV on fetal hematopoiesis resulted exclusively from an action on progenitors, or also involved the inhibition of the production of hematopoietic growth factors. PARTICIPANTS: Hematopoietic progenitors were obtained from bone-marrow aspirates of seven women of child-bearing age, from the bone marrow and liver of seven mid-trimester abortuses, and from the umbilical cord blood of seven term infants. METHODS: We added increasing concentrations of ZDV to clonal assays of hematopoietic progenitors, after which we assayed clonal maturation of progenitors, and counted the number of erythrocytes per erythroid clone and the number of neutrophils per granulocytic clone. Light-density cell fractions and enriched CD34+ progenitor fractions were studied. In other studies we determined the effect of increasing concentrations of ZDV on production of granulocyte colony-stimulating factor (G-CSF) protein [enzyme-linked immunosorbent assay (ELISA)] and mRNA by fetal and maternal monocytes, and on production of erythropoietin protein (ELISA) and mRNA by Hep3B cells. RESULTS: Mature erythroid progenitors were the most sensitive to the adverse effects of ZDV on clonal maturation, and multipotent progenitors were the most resistant. Erythroid progenitors from all fetal and neonatal sources were more sensitive to the effect of ZDV than those from the bone marrow of adult women. The inhibitory effects were explained by an action on CD34+ cells; no effect was observed on production of G-CSF or erythropoietin. CONCLUSIONS: We speculate that the low hematocrits of neonates delivered after antenatal ZDV treatment are due to reduced clonal maturation of erythroid progenitors, and that fetal erythroid progenitors are inhibited to a greater extent than maternal progenitors.

Adult↗
PubMed1996

Stability of human recombinant epoetin alfa in commonly used neonatal intravenous solutions.

OBJECTIVE: To measure epoetin alfa concentrations after adding it to a variety of commonly used neonatal intravenous fluids to determine the stability of epoetin alfa over time. DESIGN: Epoetin alfa was added to the following fluids: sterile water; NaCl 0.9%; dextrose 10% in water; dextrose 10% with albumin at concentrations of 0.01%, 0.05%, and 0.1%; and total parenteral nutrition solution containing either 0.5% or 2.25% amino acids. The fluid was administered through intravenous tubing, a T-connector, and catheter, and samples were collected at 0, 2, 4, 8, and 24 hours. MAIN OUTCOME MEASURES: Epoetin alfa concentrations were compared with the measured original preinfusion concentration and recorded as the percentage recovered. RESULTS: Concentrations declined significantly in all fluids containing less than 0.05% protein, but remained stable over 24 hours in fluids containing 0.05% or more protein. CONCLUSIONS: We conclude that epoetin alfa should be mixed in intravenous fluids containing at least 0.05% protein.

Drug Stability↗
PubMed1996

Erythropoietin receptors are expressed in the central nervous system of mid-trimester human fetuses.

Recombinant erythropoietin (rEpo) is an effective treatment for infants with the anemia of prematurity. rEpo was previously thought to act only on erythroid progenitor cells, but evidence now indicates that certain nonerythroid cells also express functional erythropoietin receptors (Epo-R). Such receptors have been observed on cells in the developing murine brain and spinal cord. The objective of this study was to determine whether Epo-R are expressed in the CNS of mid-trimester human fetuses. For this study, spinal cords were collected from five mid-trimester abortuses. RNA was extracted from the washed specimens, and the presence of Epo-R mRNA was sought by reverse transcription followed by polymerase chain reaction. Immunohistochemistry was then used to determine the anatomic location of the cells expressing Epo-R within the fetal spinal cord. The results showed that all fetal spinal cords tested contained Epo-R mRNA. The cells expressing Epo-R were radiating from the ependymal canal toward the anterior and posterior median sulci. We conclude that Epo-R are expressed on cells in the developing human CNS. Further studies are needed to determine whether they are clinically relevant in the premature infant.

Embryonic and Fetal Development↗
PubMed1996

Effect of recombinant granulocyte colony-stimulating factor on erythropoiesis in the human fetus and neonate.

Administration of large doses of recombinant granulocyte colony-stimulating factor (rG-CSF) to mice results in diminished erythropoiesis. Hyporegenerative anemia does not occur in adult humans as a consequence of treatment with rG-CSF, but it is not clear whether this will be a problem in neonates. Because rG-CSF is currently being tested as a treatment for neutropenia in neonates, we assessed the possibility that such treatment will diminish their erythropoiesis. To do this, we added rG-CSF, in vitro, to clonogenic cultures of hematopoietic progenitors obtained from the bone marrow and liver of seven human fetuses and from the umbilical cord blood of five term and five preterm infants. The range of rG-CSF concentrations tested (0.1-10.0 ng/mL) included the peak concentrations measured in the blood of neonates receiving rG-CSF treatment on experimental protocols. Inclusion of rG-CSF in the cultures did not diminish clonal maturation of fetal erythroid (erythroid colony-forming and burst-forming unit) progenitors, nor did it reduce the number of normoblasts generated per erythroid progenitor cell colony. On the basis of these studies we predict that administration of rG-CSF to neonates will not result in down-modulation of erythropoiesis.

Animals↗
PubMed1995

Epoetin alfa therapy in infants awaiting heart transplantation.

OBJECTIVE: To determine the safety and efficacy of epoetin alfa therapy in infants awaiting heart transplantation to minimize the need for blood transfusions. DESIGN: Prospective case series analysis. SETTING: Pediatric tertiary care center. PATIENTS: Eleven term infants (4 to 54 days old) awaiting heart transplantation. INTERVENTION: Infants received 16 courses of daily epoetin therapy and four subsequent courses of alternate-day epoetin therapy. RESULTS: Daily epoetin therapy was instituted at 23.6 +/- 4.5 days of age, and the duration of treatment was 13.8 +/- 3.9 days (mean +/- SEM). During daily epoetin therapy, the hematocrit increased from 0.42 +/- 0.015 to 0.50 +/- 0.019 (P < .001), and the reticulocyte count increased from 58 +/- 9 x 10(-3) to 105 +/- 16 X 10(-3) (P < .05). There were no significant changes in leukocyte count (13.4 +/- 1.0 X 10(9)/L vs 15.1 +/- 0.9 X 10(9)/L), platelet count (402 +/- 43 X 10(9)/L vs 387 +/- 39 X 10(9)/L), or creatinine (53 +/- 9 mumol/L [0.6 +/- 0.1 mg/dL] vs 53 +/- 9 mumol/L [0.6 +/- 0.1 mg/dL]) (not significant). Four patients received blood transfusions during daily epoetin therapy, but the amount of blood administered to patients was significantly less (0.9 +/- 0.5 mL/kg per day) than the phlebotomy losses (1.8 +/- 0.4 mL/kg per day) (P < .01). During alternate-day epoetin therapy, the hematocrit decreased from 0.53 +/- 0.014 to 0.43 +/- 0.019 (P < .05). CONCLUSIONS: Daily epoetin therapy appears to be effective in maintaining stable hematocrit in infants awaiting heart transplantation, who generally require multiple transfusions secondary to iatrogenic blood losses.

Anemia↗
PubMed1995

Maternal and umbilical serum concentrations of granulocyte colony-stimulating factor and its messenger RNA during clinical chorioamnionitis.

OBJECTIVE: To determine whether women with chorioamnionitis developed elevated serum granulocyte colony-stimulating factor (G-CSF) concentrations and, if so, whether the G-CSF crossed to the fetus. METHODS: We quantified G-CSF before, during, and after delivery and in the cord blood of 12 women with clinical chorioamnionitis and 12 matched controls. We also measured G-CSF messenger RNA (mRNA) transcripts in mononuclear cells isolated from maternal and cord blood at delivery. RESULTS: At study entry, G-CSF concentrations were much higher in women with chorioamnionitis (1397 +/- 950 pg/mL, mean +/- standard error of mean) than in controls (17 +/- 5 pg/mL, P < .05). At delivery, concentrations had increased in both groups (2752 +/- 1100 pg/mL in the chorioamnionitis group, 165 +/- 61 pg/mL in controls; P < .05). After delivery, G-CSF concentrations had diminished to 839 +/- 594 pg/mL in women with chorioamnionitis and to 83 +/- 16 pg/mL in controls (P < .05). Concentrations in the cord blood were 2729 +/- 974 pg/mL for the chorioamnionitis group and 51 +/- 17 pg/mL for controls (P < .05). Granulocyte colony-stimulating factor mRNA transcripts were more abundant in women with chorioamnionitis than in controls but were scarce in all matched cord blood samples tested. CONCLUSION: Serum G-CSF concentrations were elevated during clinical chorioamnionitis, and similar levels were found in maternal and cord serum. Because G-CSF mRNA levels were very low in cord mononuclear cells, the G-CSF in cord serum might be maternal in origin.

Adult↗
PubMed1995

Efficacy and cost analysis of treating very low birth weight infants with erythropoietin during their first two weeks of life: a randomized, placebo-controlled trial.

OBJECTIVE: We hypothesized that using a higher dose of erythropoietin (Epo) and starting treatment on the first day of life would reduce the transfusion requirements of ventilator-dependent and non-ventilator-dependent very low birth weight (VLBW) infants. Moreover, we hypothesized that this treatment would be cost-effective. METHODS: We randomly assigned 20 ill newborn VLBW infants to receive either Epo (200 units/kg per day) or placebo during their first 2 weeks of life. The caregivers were unaware of the treatment assignments, and erythrocyte transfusions were administered according to hematocrit and signs of anemia. RESULTS: On day 1, reticulocyte counts and hematocrits were similar in the two groups. During the subsequent 2 weeks, reticulocyte counts of the placebo recipients fell significantly below those of the Epo recipients, but hematocrits in the two groups did not differ. More transfusions were received by the placebo recipients (mean = 1.4 per patient) than by the Epo recipients (mean = 0.2 per patient; p < 0.01). No adverse effects of Epo were noted, and the costs in the placebo group exceeded those in the Epo group. CONCLUSIONS: We conclude that administration of Epo to VLBW infants during the first 2 weeks of life results in fewer transfusions and is cost-effective.

Cost-Benefit Analysis↗
PubMed1995

Neutrophil pool sizes and granulocyte colony-stimulating factor production in human mid-trimester fetuses.

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-1 alpha 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 adults. Thus, the liver of the mid-trimester human fetus is almost devoid of neutrophils, and the bone marrow contains a significantly lower proportion of neutrophils than does the marrow of term neonates or adults. These findings correlate with IL-1 alpha-induced production of G-CSF in these organs.(ABSTRACT TRUNCATED AT 250 WORDS)

Abortion, Induced↗
PubMed1995

Neutropenia in the neonate.

Neutropenia, a below normal concentration of neutrophils in the circulating blood, can be the kinetic result of diminished neutrophil production, excessive neutrophil margination, or accelerated neutrophil utilization and destruction. The significance of neutropenia to the well-being of the subject is dependent, in part, on the responsible kinetic mechanism. In this review of the causes of neutropenia in newborn infants, the authors examine neutrophil production and kinetics in the human fetus and newborn infant. The recognized causes of neutropenia in neonates are categorized and discussed according to their underlying kinetic mechanism.

Animals↗
PubMed1994

Possible mechanisms accounting for the growth factor independence of hematopoietic progenitors from umbilical cord blood.

Hematopoietic progenitors obtained from the bone marrow of healthy adults fail to undergo clonogenic maturation in vitro if a source of hematopoietic growth factors is not included in the culture dishes. In contrast, a fraction of similarly purified progenitors obtained from umbilical cord blood undergo clonogenic maturation even in the absence of added growth factors. We postulated that production of hematopoietic growth factors within the culture dishes containing the progenitors of umbilical cord blood origin might be responsible. We postulated further, that this production might be by non-progenitor cells co-plated along with the progenitors, or alternatively by CD34+ cells themselves, or by cells clonally derived from CD34+ cells. To test these possibilities we first assessed the effect of including in the cultures neutralizing antibody directed against various growth factors. Inclusion of anti-granulocyte macrophage colony-stimulating factor (GM-CSF) and anti-interleukin-3 (IL-3) (but not anti-IL-2) significantly reduced the growth factor independence of cord blood progenitors (P < .005 and P < .01). Inclusion of both anti-GM-CSF and anti-IL-3 almost completely ablated the spontaneous colony growth (P < .001). Inclusion of IL-10 also reduced, in a concentration-dependent fashion, the spontaneous generation of umbilical cord blood-derived colonies. Transcripts for GM-CSF and IL-3 were detected, by reverse transcriptase-polymerase chain reaction (RT-PCR), in the CD34+ cells from cord blood and from adult marrow. When plated without added growth factors, however, the CD34+ cells of adult marrow origin failed to produce colonies, whereas 6% of cord blood CD34+ cells similarly cultured did so. When these growth factor independent colonies were plucked from culture, transcripts for GM-CSF and IL-3 were identified in all. We conclude that production of GM-CSF and IL-3 occurs within culture dishes containing hematopoietic progenitors of umbilical cord origin, and that this explains some of their apparently unique features of in vitro growth.

Adult↗
PubMed1994

A randomized, placebo-controlled trial of recombinant human granulocyte colony-stimulating factor administration in newborn infants with presumed sepsis: significant induction of peripheral and bone marrow neutrophilia.

Host defenses in the human neonate are limited by immaturity in phagocytic immunity. Such limitations seem to predispose infected newborns to neutropenia from an exhaustion of the neutrophil reserve. Among the critical defects thus far identified in neonatal phagocytic immunity is a specific reduction in the capacity of mononuclear cells to express granulocyte colony-stimulating factor (G-CSF) after stimulation. However, the safety, pharmacokinetics, and biological efficacy of administration of recombinant human (rh)G-CSF to infected human newborns to compensate for this deficiency is unknown. Forty-two newborn infants (26 to 40 weeks of age) with presumed bacterial sepsis within the first 3 days of life were randomized to receive either placebo or varying doses of rhG-CSF (1.0, 5.0 or 10.0 micrograms/kg every 24 hours [36 patients] or 5.0 or 10.0 micrograms/kg every 12 hours [6 patients]) on days 1, 2, and 3. Complete blood counts with differential and platelet counts were obtained at hours 0, 2, 6, 24, 48, 72, and 96. Circulating G-CSF concentrations were determined at hours 0, 2, 6, 12, 14, 16, 18, 24, and 36. Tibial bone marrow aspirates were obtained after 72 hours for quantification of the bone marrow neutrophil storage pool (NSP), neutrophil proliferative pool, granulocyte progenitors, and pluripotent progenitors. Functional activation of neutrophils (C3bi expression) was determined 24 hours after rhG-CSF or placebo administration. Intravenous rhG-CSF was not associated with any recognized acute toxicity. RhG-CSF induced a significant increase in the blood neutrophil concentration 24 hours after the 5 and 10 micrograms/kg doses every 12 and 24 hours and it was sustained as long as 96 hours. A dose-dependent increase in the NSP was seen following rhG-CSF. Neutrophil C3bi expression was significantly increased at 24 hours after 10 micrograms/kg every 24-hour dose of rhG-CSF. The half-life of rhG-CSF was 4.4 +/- 0.4 hours. The rhG-CSF was well tolerated at all gestational ages treated. The rhG-CSF induced a significant increase in the peripheral blood and bone marrow absolute neutrophil concentration and in C3bi expression. Future clinical trials aimed at improving the outcome of overwhelming bacterial sepsis and neutropenia in newborn infants might include the use of rhG-CSF.

Bone Marrow↗
PubMed1994

Erythropoietin production by macrophages from preterm infants: implications regarding the cause of the anemia of prematurity.

In the human fetus, liver macrophages appear to be the primary source of erythropoietin (Epo). Epo production shifts from the liver to peritubular cells in the kidney sometime during the 3rd trimester. Some preterm infants experience a hyporegenerative anemia that appears to be caused by inadequate Epo production. It is not clear whether this anemia is due to deficient Epo production by liver macrophages or renal peritubular cells. To assess this situation, we measured Epo mRNA and protein in macrophages obtained from cord blood of preterm and term infants and from peripheral blood of adults. Macrophages from preterm infants generated Epo mRNA and protein as effectively as those from term infants and adults. It appears that the anemia of prematurity is not due to defective Epo production by macrophages.

Adult↗
PubMed1994

Effect of recombinant stem cell factor on clonogenic maturation and cycle status of human fetal hematopoietic progenitors.

Studies were undertaken to delineate the actions of stem cell factor (SCF) on human fetal hematopoietic progenitors in vitro. Mononuclear cells from umbilical cord blood of term fetuses were "panned" immunologically, and the resulting hematopoietic progenitors were grown in methylcellulose culture containing various concentrations of SCF alone or in combination with other recombinant hematopoietic growth factors. Neutralizing antibodies to IL-3 and granulocyte-macrophage colony-stimulating factor were added to all plates to which recombinant IL-3 or granulocyte-macrophage colony-stimulating factor were not included to decrease any confounding effect resulting from production of small quantities of these factors within the culture plates. SCF, as a single agent, supported clonogenic maturation of fetal granulocyte-macrophage progenitors (granulocyte-macrophage colony-forming unit, p < 0.05), multipotent progenitors (CFU-MIX, p < 0.05), and erythroid progenitors (erythroid burst-forming unit, p < 0.05). When combined with subplateau concentrations (0.1 microgram/L) of IL-3 or granulocyte-macrophage colony-stimulating factor, SCF had an additive or synergistic effect on clonogenic maturation of granulocyte-macrophage colony-forming unit and CFU-MIX. When combined with higher concentrations (5.0 micrograms/L) of IL-3 or granulocyte-macrophage colony-stimulating factor, SCF generally did not enhance colony formation but did increase the number of cells per colony. Like other pleiotropic cytokines such as IL-6, IL-9, and IL-11, SCF had a broad spectrum of action of fetal hematopoietic progenitors.

Cell Cycle↗
PubMed1993

Production of granulocyte colony-stimulating factor in vitro by monocytes from preterm and term neonates.

We postulated that defective generation of granulocyte colony-stimulating factor (G-CSF) by cells of newborn infants might underlie their deficiencies in upregulating neutrophil production and function during bacterial infection. To test this, we isolated monocytes from the blood of preterm neonates, term neonates, and adults and, after stimulation with various concentrations of interleukin-1 alpha (IL-1 alpha) or lipopolysaccharide (LPS), quantified G-CSF concentrations in cell supernatants and G-CSF mRNA in cell lysates. When stimulated with plateau concentrations of IL-1 alpha for 24 hours, G-CSF concentrations were higher in supernatants of adult cells (8,699 +/- 5,529 pg/10(6) monocytes) than in those from term infants (2,557 +/- 442 pg, P < .05) or from preterm infants (879 +/- 348 pg, P < .05 v adults). When stimulated with plateau concentrations of LPS, supernatants of monocytes from preterm neonates had less G-CSF than did those from term neonates or adults. G-CSF mRNA content was low in cells from preterm infants, higher in those from term infants, and highest in those from adults. On the basis of the in vitro studies, we speculated that serum G-CSF concentrations might be less elevated in neutropenic neonates than in neutropenic adults. Indeed, serum concentrations were relatively low in all nonneutropenic subjects; 92 +/- 34 pg/mL (mean +/- SEM) in 10 preterm neonates, 114 +/- 21 pg/mL in 16 term neonates, and 45 +/- 13 pg/mL in 11 healthy adults. Serum concentrations were not elevated in 7 neutropenic neonates (39 +/- 17 pg/mL) but were in 8 neutropenic adults (2101 +/- 942 pg/mL, P < .05 v healthy adults). Other studies suggested that the lower G-CSF production in neonates is not counterbalanced by a heightened sensitivity of G-CSF--responsive progenitors to G-CSF. Therefore, we speculate that newborn infants, particularly those delivered prematurely, generate comparatively low quantities of G-CSF after inflammatory stimulation, and that this might constitute part of the explanation for their defective upregulation of neutrophil production and function during infection.

Adult↗