Cytokine expression of cord and adult blood mononuclear cells in response to Streptococcus agalactiae

Neonatal bacterial sepsis is often characterized by a fulminant clinical course and highly elevated plasma levels of proinflammatory cytokines. To evaluate in vitro activation of the neonatal immune system by specific infectious stimuli, cord blood cells from healthy neonates were examined for expression of tumor necrosis factor-alpha (TNF-alpha), IL-1beta, IL-6, and IL-8 in response to Streptococcus agalactiae (GBS), lipopolysaccharide (LPS), and lipoteichoic acid (LTA). Cytokine-expression was compared in mononuclear cells from cord and adult peripheral blood. TNF-alpha and IL-6 levels in the supernatant of cord blood cell cultures were significantly higher after stimulation with heat-killed GBS (10(7)/mL) than with LPS (2 microg/mL) or LTA (2 microg/mL) (TNF-alpha: 2215 versus 267.5 versus 40 pg/mL, p = 0.001; IL-6: 9667 versus 4909 versus 919 pg/mL, p = 0.006). mRNA expression of TNF-alpha, IL-1beta, IL-6, and IL-8 was equally pronounced after stimulation with either GBS, LPS, or LTA in cord or adult blood cells at various times. A MAb directed against the monocyte receptor molecule CD14 did not inhibit the release of cytokines in cord blood mononuclear cells after stimulation with GBS. In summary, activation of cord blood cells by infectious stimuli is comparable to the adult immune response in terms of expression of proinflammatory cytokines. GBS in particular proves to be a potent activator of the neonatal immune system when compared with LPS and LTA. CD14 seems not to be a crucial molecule for activation of cord blood cells by GBS.     

Association of development of chronic lung disease of newborns with neonatal colonization of Ureaplasma and cord blood interleukin‐8 level

Background: The aim of the present study was to investigate the association of chronic lung disease (CLD), neonatal Ureaplasma colonization, and interleukin‐8 (IL‐8) level of cord blood in preterm infants. Methods: In 77 infants of <32 weeks gestation, the relationship between IL‐8 level of cord blood, neonatal colonization of Ureaplasma, histological chorioamnionitis (CAM), and development of CLD was studied. Results: Five infants died and 29 infants developed CLD. The CLD group had significantly lower gestation (mean ± SD: 26.6 ± 1.8 weeks) compared with the infants without CLD (28.9 ± 1.9 weeks, P < 0.0001). Logistic analysis showed that the development of CLD was associated with gestational age (odds ratio [OR], 0.5; 95% confidence interval (CI): 0.4–0.8) and Ureaplasma colonization (OR, 4.1; 95%CI: 1.2–14.4). Ureaplasma colonization was also associated with CAM (OR, 6.5; 95%CI: 1.8–23.5), absence of respiratory distress syndrome (OR, 6.2; 95%CI: 1.3–30.5), and development of CLD (OR, 4.0; 95%CI: 1.1–15.3). Elevated cord blood IL‐8 ≥100 pg/mL was associated with female sex and the isolation of microorganisms (OR, 49.4; 95%CI: 4.6–525). Conclusion: The development of CLD defined by oxygen requirement at 36 weeks was associated with neonatal Ureaplasma colonization but not with IL‐8 level of cord blood. Elevated cord blood IL‐8 was associated with neonatal microorganisms isolation.     

Defective interferon gamma production in neonatal T cells is independent of interleukin-2 receptor binding.

Newborns are more susceptible to fungal, viral, protozoan, and certain bacterial infections than adults. This susceptibility is due in part to a decreased interferon gamma (IF gamma) production. The present investigation focuses on the role of the IL-2 receptor in the deficient IF gamma production in neonatal T cells. IL-2-induced IF gamma production in unstimulated neonatal cord blood and adult peripheral T cells was comparable, but the IF gamma production in CD3-stimulated neonatal T cells was only 20% of the adult production. Neonatal and adult T cells showed no difference in the expression of the 55-kD alpha and 75-kD beta chains of the IL-2 receptor. Blocking of the 55-kD alpha chain of the IL2 receptor with TAC MAb resulted in a marginal reduction in IF gamma release from unstimulated or CD3-stimulated neonatal T cells cultured in the presence of IL-2. In contrast, blocking of the 55-kD alpha chain of the IL-2 receptor in adult T cells caused a 92% and 73% inhibition in IF gamma production in unstimulated and stimulated T cells, respectively. Blocking of the 75-kD beta chain of the IL-2 receptor with TU27 MAb had a marginal effect in both unstimulated and CD3-stimulated neonatal and adult lymphocytes. Binding studies with unstimulated cord blood T cells using [125I]-IL-2 showed a binding affinity that corresponded with the intermediate affinity IL-2 receptor. In CD3-stimulated cord blood T cells, a high-affinity receptor was found.(ABSTRACT TRUNCATED AT 250 WORDS)     

Young patients with both type 1 diabetes mellitus and asthma have a unique IL-12 and IL-18 secretory pattern

Rachmiel M, Bloch O, Shaul AA, Ben‐Yehudah G, Bistritzer Z, Weintrob N, Ofan R, Rapoport MJ. Young patients with both type 1 diabetes mellitus and asthma have a unique IL‐12 and IL‐18 secretory pattern. Background: The expression of the regulatory cytokines interleukin (IL)‐12 and IL‐18 in patients with both Th1‐ and Th2‐mediated diseases, type 1 diabetes mellitus (T1DM) and asthma, is unknown. Objective: To investigate the in vivo and in vitro IL‐12 and IL‐18 secretion patterns in patients with both T1DM and asthma. Methods: Peripheral blood mononuclear cells (PBMC) were collected from 44 patients. Mean age 19.4 ± 4.7 yr (10.5–28 yr), divided into four paired groups: T1DM and asthma, asthma only, T1DM only, and healthy controls. T‐cell proliferative response was assessed. IL‐12 and IL‐18 serum levels and expression by PBMC following in vitro stimulation by lipopolysaccharide (LPS) were determined by enzyme‐linked immunosorbent assay (ELISA). Results: Patients with T1DM and asthma had higher serum levels of both IL‐12 and IL‐18 compared to controls: 146.2 ± 69.2 and 109.7 ± 34.6 pg/mL, p = 0.038 and 436.1 ± 117.9, 320.2 ± 99.1 pg/mL, p = 0.028, respectively. Stimulated IL‐12 secretion was significantly lower in these patients compared to those with one disease only: 809 ± 426.4, 2111.6 ± 2214.3, 3188.1 ± 2692.9 pg/mL and after 48 h: 956.3 ± 489.3, 2429.8 ± 2394.6, 3874.5 ± 2820.3 pg/mL, respectively, p < 0.03 for all. The IL‐18/IL‐12 serum ratio was also significantly higher in patients with both diseases compared to those with asthma only, p = 0.017. Conclusion: Patients with both T1DM and asthma display a different pattern of IL‐12 and IL‐18 expression compared to patients with one disease only and controls.     

Differences in adhesion receptor expression between immature and older platelets and red blood cells of neonates and adults

PURPOSE: To examine the hypothesis that reticulated platelets and reticulocytes show elevated adhesion receptor expression compared with mature cells in both adult and neonatal cells. METHODS: Flow cytometry was used to examine laminin, fibronectin (VLA-6), and thrombospondin (glycoprotein IV [GPIV]) expression in reticulated red cells, reticulated platelets, and older peripherally circulating mature red cells and mature platelets in seven newborn cord blood samples and blood samples from eight adult volunteers. RESULTS: The difference in the neonatal reticulated platelet percentage of 9.2+/-14.8% was not statistically significant from the adult reticulated platelet percentage of 5.0+/-1.5% in this small population. There was a statistically significant difference between the reticulated cord blood red cell mean of 7.7+/-1.8% and the adult mean of 3.1+/-0.43%. Mean expression of VLA-6 was 96% in adult reticulated platelets, 79% in adult mature platelets, 81% in cord reticulated platelets and 65% in cord mature platelets. Mean expression of GPIV was similar, with corresponding values of 90%, 71%, 78%, and 57%. Reticulated red cells in adults averaged 44% VLA-4 and 46% GPIV; cord reticulocytes were 9% and 15%, respectively. CONCLUSIONS: Reticulated cells newly released from the bone marrow express more adhesive receptors than mature cells in both groups. Cord blood samples showed hypoexpression of both receptor types in red blood cells and platelets.     

Neonatal blood glucose concentrations in caesarean and vaginally delivered term infants

Background: Little is known about the glucose concentrations at and after birth of infants delivered by caesarean section (CS), when compared with infants born vaginally (VD). Aim: To compare venous cord blood glucose concentrations of term infants born after elective CS to infants born by VD. We studied the null hypothesis that mode of delivery does not affect neonatal blood glucose values. Methods: We compared cord blood glucose concentrations in healthy term infants born after VD (n = 16) or by elective CS (n = 21). Glucose concentrations were obtained immediately at birth from the umbilical cord. Kruskal–Wallis was used to compare glucose concentrations and demographic variables between the groups. Results: Gestational age was 39.6 ± 0.8 weeks in VD group vs. 38.7 ± 0.9 weeks in CS group, and birthweight was 3359 ± 494 vs. 3500 ± 528 g. Cord blood glucose concentration was higher in VD (81.3 ± 16.9 mg/dL) than CS infants (70.3 ± 9.7 mg/dL, p = 0.039). The change in blood glucose concentration over the first 2‐h of life differed significantly between the two groups, being an increase in CS versus a decrease in VD infants (?3.5 ± 15.2 vs. ?15.4 ± 24.6 mg/dL, p = 0.013). Conclusions: Glucose concentrations in VD infants are higher than in infants born by elective CS without labour.     

Fc and complement receptor (CR1 and CR3) expression on neonatal human polymorphonuclear leukocytes

Fc gamma receptor III (Fc gamma RIII) and complement receptors (CR1 and CR3) were examined on polymorphonuclear leukocytes (PMN) from neonatal cord blood and adult blood using monoclonal antibodies directed against these receptors. Receptor expression was determined by flow cytometry. Fc gamma RIII, CR1 and CR3 expression was examined in whole blood at 4 degrees C, at 37 degrees C with or without stimulation with the chemotactic peptide f-met-leu-phe, and on PMN isolated by Ficoll-Hypaque centrifugation and dextran sedimentation. There was no significant difference between adult and cord PMN in the percent of cells which expressed Fc gamma RIII, CR1 and CR3 when examined in whole blood at 4 or 37 degrees C, or following stimulation with f-met-leu-phe. The percentage of PMN expressing CR1 and CR3 was lower on cord PMN compared to adult PMN when these cells were examined following Ficoll-Hypaque centrifugation and dextran sedimentation. The mean peak fluorescence of PMN which stained positively for CR1 and CR3 increased following f-met-leu-phe treatment of whole blood from adults and neonates. Since neonatal cord PMN were capable of upregulating complement receptors in response to chemotactic factors these results do not explain the increased susceptibility to infection exhibited by neonates.     

Effects of ciclosporin A, tacrolimus and sirolimus on cytokine production in neonatal immune cells

BACKGROUND: It was the aim of this study to evaluate the effects of the well-known immunosuppressive drugs ciclosporin A (CsA), tacrolimus and sirolimus on the intracytoplasmic cytokine expression of neonatal immune cells. METHODS: Immunosuppressive drugs were added to whole blood cultures of neonatal cord blood samples (n = 17) and peripheral blood samples of adults (n = 17) in vitro prior to stimulation of lymphocytes with phorbol 12-myristate 13-acetate (PMA)/ionomycin or monocytes. RESULTS: Upon exposure to ciclosporin A (500 ng/mL) or tacrolimus (25 ng/mL) the number of cytokine expressing T cells was almost completely blocked in neonatal T cells while sirolimus (10 ng/mL) only inhibited intracytoplasmatic tumour necrosis factor alpha (TNF-alpha) expression (mean% positive cells; 4.0 +/- 2.1% vs. 1.09 +/- 0.6%, p = 0.003), but mildly stimulated the intracellular expression of interleukin (IL)-2 (24.4 +/- 6.5% vs. 28.1 +/- 7.1%, p = 0.041). In cord blood lymphocytes, the inhibitory effect of ciclosporin A and tacrolimus was dose-dependent (e.g. IL-2: control, 12.3 +/- 5.33%, ciclosporin A 5 ng/mL, 10.1 +/- 5.5%; 50 ng/mL, 7.1 +/- 4.7%; 500 ng/mL, 1.2 +/- 0.3%; tacrolimus 0.25 ng/mL, 9.3 +/- 4.9%; 2.5 ng/mL, 6.1 +/- 3.3%; 25 ng/mL, 1.0 +/- 0.6%), while the function of adult lymphocytes was only impaired at high doses of both compounds. In contrast, the number of cytokine expressing monocytes was not influenced by ciclosporin A and tacrolimus except for a minor decrease of TNF-alpha producing neonatal monocytes after addition of tacrolimus (17.9% vs. 13.9%, p = 0.031). Interestingly, sirolimus was shown to inhibit intracellular IL-6 production in adults (63.1 +/- 12.7% vs. 52.0 +/- 16.0%, p = 0.005), but in neonatal monocytes intracellular IL-6 expression was stimulated (53.5 +/- 22.0% vs. 64.7 +/- 19.1%, p = 0.041). CONCLUSIONS: The potent dose-dependent inhibitory effect of ciclosporin A and tacrolimus in cord blood lymphocytes provides the basis for further studies on functional immaturity of the neonatal immune system and for future strategies to optimize umbilical cord blood transplantion. Sirolimus was demonstrated to have a distinct effect on neonatal immune cells as shown by increased expression of IL-2 in lymphocytes and IL-6 in monocytes, while only lymphocytic TNF-alpha expression was inhibited.     

新生猪溶血性黄疸模型的制备与验证

目的 建立新生猪溶血性黄疸动物模型,以进一步研究新生儿溶血性黄疸的病理生理。方法 7日龄纯种大约克白猪分成实验组和对照组,每组各6只。并采用免疫新西兰大白兔的方法 制备兔抗猪红细胞抗体,分离兔抗猪红细胞血清。实验组静脉注射兔抗猪红细胞血清5mL,对照组注射5mL生理盐水。两组均每6h采血送检血常规及肝功能。结果 实验组注射兔抗猪红细胞血清18h后血清胆红素水平高于对照组(64±30μmol/Lvs20±4μmol/L,PP12/L,低于对照组[(5.09±0.44)×1012/L](P12/L]和HB(87±3g)进一步降低,低于对照组[(5.11±0.39)×1012/L,97±6g](P结论 新生猪溶血性黄疸模型较好地模拟了人类溶血性黄疸的病理过程,为更进一步研究新生儿溶血病提供了良好的生物物质基础。     

Thymic size correlates with cord blood zinc levels in low-birth-weight newborns

Thymus is essential for immunity as it provides environment for T cell differentiation and maturation. There is limited information on various factors which determine thymic size at birth. We studied the influence of cord blood zinc and copper levels and maternal and neonatal nutritional status on thymic size in term low-birth-weight (LBW) newborns. A prospective observational study on 44 term LBW (<2,500 g) newborns (cases) and 71 gestational age-matched newborns weighing ≥2,500 g (controls). Sonographically determined thymic index was correlated to cord blood zinc and copper levels and maternal and neonatal nutritional status. Thymic index measured 3.74?±?1.57 cm³ in LBW newborns compared to 4.90?±?2.33 cm³ in normal-birth-weight newborns. Thymic index was significantly correlated to cord blood zinc levels but not to cord blood copper levels and had linear relationship to the maternal body mass index and midarm circumference and neonatal anthropometric parameters. Conclusion: Thymic index is linearly related to cord blood zinc levels and maternal and neonatal nutritional status. Compared to thymic size in the Western newborns, the thymus is less than half in size in Indian newborns of normal birth weight. Reduced thymic size in Indian newborns in general and LBW infants in particular may have consequences for their immune competence and the risk of infections. Improving nutrition of pregnant women, particularly zinc nutriture might favorably influence thymic size in their offspring.     

Comparison of generic tacrolimus and Prograf drug levels in a pediatric kidney transplant program: Brief communication

Abdulnour HA, Araya CE, Dharnidharka VR. Comparison of generic tacrolimus and Prograf drug levels in a pediatric kidney transplant program: Brief communication.
Pediatr Transplantation 2010: 14:1007–1011. © 2010 John Wiley & Sons A/S. Abstract: A generic version of tacrolimus was approved for use in the USA in August 2009. These narrow therapeutic index generics are tested for bioequivalence only in adults. No data are available on generic tacrolimus levels in children with allografts. Four patients with stable renal allografts in our pediatric program were inadvertently switched to generic tacrolimus. We retrospectively analyzed pre‐ and post‐switch trough tacrolimus and serum creatinine levels. Twelve‐h trough tacrolimus levels (mean ± s.e.) were (i) patient 1 (12‐yr‐old girl): 7.0 ± 0.69 and 9.7 ± 3.5 (p = NS); (ii) patient 2 (eight‐yr‐old boy): 4.7 ± 0.68 and 3.4 ± 0.84 (p = 0.04); (iii) patient 3 (22‐yr‐old woman): 6.8 ± 0.17 and 6.6 ± 0.4 (p = NS); (iv) patient 4 (20‐yr‐old woman): 5.4 ± 0.25 and 4.9 ± 1.4 (p = NS). Creatinine levels were similar pre‐ and post‐switch (eGFR > 75 mL/min/1.73 m²) in the first three. Patient 4 experienced a biopsy proven acute rejection immediately after switching. Mean creatinine rose from 1.15 ± 0.05 to 2.168 ± 0.07 after switch (p < 0.001). Given our mixed picture with the early data, we suggest careful monitoring of pediatric patients who get switched to generic tacrolimus.     

Possible pathologenic role of interleukin-5 and eosino cationic protein in Henoch-Schönlein purpura nephritis

Abstract Background : The mechanism for the onset of Henoch‐Schönlein purpura nephritis is unknown. In order to identify the pathogenesis of nephritis, laboratory findings and serum cytokines between Henoch‐Schönlein purpura (HSP) patients without nephritis and with nephritis were investigated. Methods : We enrolled 32 patients who had been diagnosed with HSP from January 1993 to December 1998. These patients were divided into two groups. Group 1 consisted 12 patients without nephritis and group 2 consisted 20 patients with nephritis. We evaluated laboratory findings such as eosinophil counts, serum IgE, eosino cationic protein (ECP), and serum cytokine (interleukin (IL)‐2, IL‐4, IL‐5, IL‐6, IL‐10, IL‐13 interferon‐γ and tumor necrotic factor‐α) concentrations between both groups. Results : At the acute phase, serum IL‐5 and ECP concentrations in group 2 were higher than those in group 1 (59.4 ± 32.7 pg/mL vs. 10.8 ± 12.8 pg/mL, P < 0.05, 24.3 ± 5.1 µg/L vs. 8.9 ± 4.2 µg/L, P < 0.05, respectively). Serum IL‐4 concentrations at the acute phase in group 1 were higher than those in group 2 (40.2 ± 21.5 pg/mL vs. 10.7 ± 5.4 pg/mL, P < 0.01). In group 2, serum IL‐5 concentrations at the acute phase were higher than those at recovery phase. Conclusions : These findings suggest that IL‐5 and eosinophil activation may be one of the factors involved in the mechanism for onset of nephritis.     

Granulocyte functions and changes in ability with age in newborns; Report no. 2: Activation of granulocyte functions by cytokines

BACKGROUND: The aim of the present study was to examine the function of granulocytes in newborns from the perspective of granulocyte activation by cytokines. METHODS: Granulocytes were stimulated with tumor necrosis factor-alpha, granulocyte-macrophage colony stimulating factor (GM-CSF) or granulocyte colony stimulating factor, and the reactivity of granulocytes to these substances was then compared between newborns (umbilical cord blood, peripheral blood obtained at age 5 days and at age 1 month) and peripheral blood obtained from adults. In addition, the expression of cytokine receptors on the surface of granulocytes was measured for each age group. RESULTS: The amplification of CD11b expression on the surface of granulocytes and suppression of l-selectin expression were weaker for cord blood regardless of which cytokine was added. In addition, the increases in the activity of intracellular elastase when stimulated with tumor necrosis factor-alpha or GM-CSF were significantly lower for cord blood. Moreover, the expression of GM-CSF receptors and granulocyte colony stimulating factor receptors on the surface of granulocytes was lower for cord blood, and this expression approached the level found in adults as age increased. CONCLUSION: Granulocytes during early infancy exhibit low reactivity to inflammatory cytokines, and this was considered to be one of the factors contributing to the higher incidence of serious bacterial infections in infants.     

Efficacy of two different doses of oral vitamin D supplementation on inflammatory biomarkers and maternal and neonatal outcomes

Hypovitaminosis D during pregnancy is suggested to have a link with complications in both mother and infant. We aimed to evaluate the efficacy of two doses of vitamin D3 supplementation during pregnancy on maternal and cord blood vitamin D status, inflammatory biomarkers, and maternal and neonatal outcomes. A total of 84 pregnant women (gestational age of <12 weeks) were randomly allocated to one of two groups: (a) 1,000‐IU/d vitamin D and (b) 2,000 IU/d. Biochemical assessments (25‐hydroxycalciferol (25(OH)D), hs‐CRP, and cell‐culture supernatant concentrations of IL‐1β, IL‐6, and TNF‐α) of mothers were performed at the beginning and 34 weeks of gestation. Assessments of infants at delivery comprised cord blood serum concentrations of 25(OH)D, hs‐CRP, IL‐1β, IL‐6, TNF‐α, birth sizes, and Apgar score. Circulating concentrations of 25(OH)D increased in both intervention groups with more increment in 2,000 IU/d than in 1,000 IU/d (46.7 ± 30.7 vs. 24.0 ± 21.07 nmol L^?1, P = .001). Concentrations of TNF‐α decreased significantly in group 2,000 (?913.1 ± 1261.3 ng L^?1, P = .01). The cord blood concentration of IL‐6 in group 2,000 IU/d, compared with 1,000 IU/d, was significantly lower (25.9 ± 32.0 vs. 4.6 ± 1.4 ng L^?1, P = .03). The birth sizes including weight, length, and head circumference of the infants of group 2,000 IU/d were significantly higher than the infants' of group 1,000 IU/d. Supplementation with 2,000‐IU/d vitamin D3 is more effective than 1,000 IU/d in pregnant women in terms of increasing circulating 25(OH)D, ameliorating pro‐inflammatory markers notably TNF‐α in mother and IL‐6 in cord blood, and improving neonatal outcomes including the birth sizes.     

Heart rate variability during respiratory pauses in puppies and dogs

Because increased complement receptor expression is necessary for optimal function of adult neutrophils, we tested the hypothesis that the increased susceptibility of neonates to infection might be due to an impaired ability of neonatal neutrophils to increase expression of complement receptors in response to chemotactic stimuli. We used monoclonal antibodies and flow cytometry to compare surface expression of the receptors for the complement components C3b (CR1) and C3bi (CR3) on adult and neonatal cord blood neutrophils (PMNs). We also compared receptor expression on PMNs from infants delivered by cesarean section without labor versus infants delivered vaginally. Expression of both CR1 and CR3 was minimal on resting adult and neonatal PMNs maintained at 0 degrees C. There was a modest increase in expression of both receptors when PMNs were warmed to 37 degrees C. This increase was similar on adult and neonatal cells, both unfractionated in whole blood and after isolation with Percoll density centrifugation, with one exception. Expression of CR1 was greater on isolated PMNs from vaginally delivered infants versus adults when the cells were warmed to 37 degrees C. This difference was not observed with cells from infants delivered by cesarean section without labor, suggesting this modest increase in receptor expression may be due to factors associated with labor. When isolated cells were stimulated with either N-formyl-methionyl-leucyl-phenylalanine or zymosan-activated serum, expression of CR1 increased to the same extent in both neonatal and adult PMNs. In contrast, maximal CR3 expression on cord PMNs stimulated with N-formyl-methionyl-leucyl-phenylalanine or zymosan-activated serum was only 75% of the adult values.(ABSTRACT TRUNCATED AT 250 WORDS)     

Human Cord Blood Monocytes: Binding and Ingesting Capacity Mediated by Fc and C3b Receptors

Human cord blood monocytes have been compared to monocytes from adults. Our results show that unstimulated cord blood monocytes are as effective as monocytes from adults with regard to their binding and ingesting capacity mediated by Fc and C3b receptors. Furthermore, when stimulated with PMA (phorbol-myristate-acetate), the C3b receptor-mediated phagocytosis in cord blood monocytes was enhanced to the same extent as in monocytes from adults. These findings show that Fc and C3b receptor functions in human monocytes are fully developed at birth and cannot explain the increased susceptibility to infections seen in the neonate.     

Cytokines in umbilical cord blood and the impact of labor events in low-risk term pregnancies

Background

Inflammatory mechanisms involved in the onset and progression of labor at term may affect the fetal compartment impacting neonatal outcomes.

Study design

Umbilical cord blood collected from umbilical cords after delivery of the fetus and again after delivery of the placenta in low-risk non-laboring and laboring patients was analyzed for blood gases/pH and multiple cytokines.

Results

Umbilical cord levels of IL-6, IL-8 and IL-10 were increased 6, 2 and 1.5 fold, respectively, in laboring patients without placental inflammation, and for IL-6 and IL-8 a further 12 and 6 fold, respectively, in laboring patients showing histologic chorioamnionitis, but with no evident effect of nuchal cord with FHR decelerations, fetal acidemia, nor of labor duration. For laboring patients, umbilical vein levels of IL-10 and MIP-1α were increased compared to arterial levels indicating net flux from the placenta, while umbilical artery levels of IL-6 and IL-8 were increased compared to venous levels indicating net flux from fetal sources. Placental cord levels of IL-6, IL-10, MIP-1α and MIP-1β were also increased compared to respective umbilical cord levels, confirming placental release of these cytokines into cord blood after delivery of the fetus.

Conclusion

Labor in low-risk patients at term will result in increased cytokines in umbilical cord blood and moreso when associated with histologic chorioamnionitis with the potential to impact neonatal outcomes. IL-6 and IL-8 as the primary cytokines increased in cord blood may act synergistically in promoting the inflammatory response with labor, and are likely released from both placental and fetal tissues contributing to widespread distribution through the fetal circulation.     

急性ITP患儿外周血调节性T细胞及相关细胞因子的研究

目的检测急性特发性血小板减少性紫癜(AITP)患儿外周血CD4+CD25+调节性T细胞(regulationTcells,Tr细胞)及相关细胞因子的变化,探讨它们在AITP发病机制中的作用。方法流式细胞仪分别检测AITP患儿和正常健康儿童外周血Tr细胞的数量,ELISA法检测血清中相关细胞因子的含量,并进行相关性分析。结果AITP患儿外周血Tr细胞的数量明显低于正常对照组[(2.83±1.05)%vs(5.07±0.59)%,P<0.05];AITP患儿血清中IL-10、转化生长因子β1(TGF-β1)的含量均也低于正常对照组[IL-10:(29.48±13.69)pg/mlvs(43.10±14.95)pg/ml;TGF-β1(170.04±91.58)pg/mlvs(254.75±130.41)pg/ml,P<0.05],差异有显著性。AITP患儿外周血Tr细胞的比例与血清中IL-10、TGF-β1的含量都呈正相关(r1=0.54,r2=-0.66,P<0.05)。结论急性ITP患儿外周血中Tr细胞数量的减少及相关细胞因子含量的降低可能与急性ITP的细胞免疫失调有关。