Sepsis-induced alteration in T-cell Ca(2+) signaling in neonatal rats

Sepsis-induced suppression in T-cell proliferation follows deranged Ca(2+) signaling in adult rats. In preliminary studies, we observed suppression in T-cell proliferation in septic neonatal rats as well. In this study, we assessed splenic T-cell cytosolic Ca(2+) concentration, [Ca(2+)](i), as its elevation plays an important role in T-cell proliferation. Also, we investigated the role of PGE(2) in sepsis-related changes in T-cell [Ca(2+)](i) in animals pretreated with cyclooxygenase-1 (COX-1) inhibitor (resveratrol) and cyclooxygenase-2 (COX-2) inhibitor (NS-398). Sepsis was induced in 15-day-old rat pups by intraperitoneal implantation of fecal pellets containing Escherichia coli and Bacteroides fragilis. The sham group consisted of pups implanted with sterile fecal pellets. Septic and sham pups were sacrificed 24 h after implantation and their spleens were removed. The spleens from sham and septic pups, along with spleens from unoperated control pups, were processed for single cell suspensions, and T cells were isolated using nylon wool columns. Fura-2 fluorophotometry was employed for the measurement of [Ca(2+)](i) (in nM units) in T cells stimulated with concanavalin A (ConA). Our results show that ConA-mediated T-cell [Ca(2+)](i) response is significantly suppressed in septic neonatal rats. Pretreatment of pups with COX-2, but not COX-1 inhibitor, prevented the decrease in the [Ca(2+)](i) response. These findings suggest that PGE(2) might induce the attenuation in T-cell Ca(2+) signaling during sepsis in neonatal rats.     

COX-1 and COX-2 contributions to basal and IL-1 beta-stimulated prostanoid synthesis in human neonatal cerebral microvascular endothelial cells

Mechanisms of endothelium-dependent regulation of cerebral circulation in human neonates are poorly understood owing to the lack of experimental data. Prostanoids, the products of the cyclooxygenase (COX) pathway, appear to be important regulators of blood flow in neonates. COX activity in cultured endothelial cells from small (60-300 microm) and large (>300 microm) microvessels from the autopsy specimens of neonatal human cerebral cortex and cerebellum (22-26 wk gestational age) was detected as production of vasodilator prostanoids, prostacyclin [as 6-keto-prostaglandin (PG) F(1 alpha)] and PGE(2) from arachidonic acid. Treatment of neonatal human cerebral microvascular endothelial cells (hCMVEC) with IL-1 beta (50 ng/mL, 17 h) stimulated COX activity 5- to 20-fold. Basal and IL-1 beta-stimulated COX activities were inhibited by NS-398, indicating substantial COX-2 contribution to endothelial prostanoid synthesis in neonatal human brain cortex and cerebellum at rest and when mimicking the inflammatory conditions. Increased COX-2-linked activity in response to IL-1 beta was observed in hCMVEC from both cerebrum and cerebellum (5- to 20-fold), while under the same conditions elevated COX-1-linked activity was detected only in hCMVEC from cerebellum (5- to 10-fold). In IL-1 beta-treated hCMVEC, a shift toward PGE(2) as the major vasodilator product of the COX pathway was observed. Acute treatment with the protein tyrosine kinase inhibitor, tyrphostin 25, inhibited basal and IL-1 beta-induced COX activities, suggesting the importance of posttranslational modifications in endothelial COX-2 activation in human brain. Altogether, these data indicate that both COX-1 and COX-2 contribute to endothelial prostanoid synthesis in the neonatal human brain under basal conditions and in response to proinflammatory cytokine IL-1 beta.     

Serum leptin levels and their relationship to tumor necrosis factor-alpha and interleukin-6 in neonatal sepsis

Circulating leptin concentrations are raised in animal models of inflammation and sepsis and leptin production is also increased in rodents by administration of endotoxin or cytokines. The purpose of this study was to investigate the effect of sepsis on serum leptin concentration and whether circulating leptin was related to tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) release in newborn infants. Plasma leptin, TNF-alpha and IL-6 were measured in 20 neonates with culture-proven sepsis as soon as sepsis was diagnosed and after recovery and in 15 healthy control infants. There was no significant difference in plasma leptin levels between septic and control infants (p > 0.05); there was also no difference in plasma leptin levels in septic neonates before and after therapy (p > 0.05). No relationship between leptin and TNF-alpha (r = 0.16, p > 0.05) or IL-6 (r = 0.12, p > 0.05) was identified. These findings suggest that a major role of leptin in acute neonatal sepsis appears unlikely.     

Role of procalcitonin, C-reactive protein, interleukin-6, interleukin-8 and tumor necrosis factor-alpha in the diagnosis of neonatal sepsis

Diagnosis of neonatal sepsis may be difficult because clinical presentations are often nonspecific, bacterial cultures are time-consuming and other laboratory tests lack sensitivity and specificity. In this study, we aimed to investigate the role of procalcitonin (PCT), C-reactive protein (CRP), interleukin (IL)-6, IL-8 and tumor necrosis factor-alpha (TNF-alpha) in establishing the diagnosis and evaluating the prognosis of neonatal sepsis. Twenty-six neonates with blood-culture positivity and clinical sepsis, hospitalized for clinical suspicion of neonatal sepsis in neonatal intensive care units of Balcali Hospital, Cukurova University and Adana State Hospital between May 2000 and January 2001 (Group I) and 29 healthy neonates followed at the neonatal units and outpatient clinics of these hospitals (Group II) in the same period were studied. Among the septic neonates, 13 had early-onset (Group Ia) and 13 had late-onset (Group Ib) neonatal sepsis, while 14 of the healthy neonates had perinatal risk factors (Group IIa) and 15 of them had no risk factors (Group IIb). The demographic and clinical characteristics of the septic and healthy neonates were recorded, blood samples for determining serum PCT, CRP, IL-6, IL-8 and TNF-alpha were collected from the healthy and the septic neonates before starting treatment, and these investigations were repeated on the 3rd and 7th days of treatment. In this study, it was found that: (a) pre-treatment mean serum PCT, CRP, IL-6, IL-8 and TNF-alpha levels were significantly higher in the septic neonates than in the healthy ones, (b) compared with the pre-treatment values, serum PCT, IL-6 and TNF-alpha had progressively decreased on the 3rd and 7th days of the treatment in the 17 recovered patients, though they progressively increased in nine patients who died during treatment, (c) the area under the receiver operating characteristic (ROC) curve (AUC) for PCT, TNF-alpha, IL-6, CRP, and IL-8 were 1.00, 1.00, 0.97, 0.90 and 0.68, respectively. For the cut-off value of PCT > or = 0.34 ng/ml, the test was found to have a sensitivity of 100%, specificity of 96.5%, positive predictive value of 96.2%, negative predictive value of 100% and diagnostic efficacy of 98.3% for bacterial sepsis in neonates. For the cut-off value of TNF-alpha > or = 7.5 pg/ml, sensitivity, specificity, positive predictive value, negative predictive value and diagnostic efficacy were found to be 100%, 96.6%, 96.2%, 96.5% and 98.3%, respectively. It was detected that sensitivity, specificity and diagnostic efficacy values were lower for IL-6, CRP and IL-8. We conclude that PCT and TNF-alpha are the best markers in the diagnosis of neonatal sepsis, and these markers are also valuable in following the effectiveness of treatment and determining the prognosis of the disease.     

Dysregulation of IL-13 production by cord blood CD4+ T cells is associated with the subsequent development of atopic disease in infants.

Early intervention strategies in allergic diseases will be dependent on identification of newborns at high risk for later development of atopic disease. In this cohort study of 106 neonates, we investigated whether cytokine production property and responsiveness to IL-12 of neonatal CD4(+) T cells were associated with the subsequent development of atopic disease and whether a skewed cytokine production property was intrinsic to helper T cells. To exclude the effects of contaminating cells, highly purified cord blood CD4(+) T cells were stimulated with anti-CD3 MAb and recombinant B7-2 molecule in the presence or absence of IL-12. Production of IL-13 and interferon-gamma was determined by ELISA. The infants were assessed at 12 mo for the development of atopic diseases. CD4(+) T cells of neonates who manifested allergic symptoms (atopic group) produced higher levels of IL-13 compared with those of the nonatopic group in both the presence and absence of IL-12. No significant difference was noted between the two groups with respect to interferon-gamma production. Moreover, higher IL-13 production was also observed in neonates with chronic eczema than those with short-term eczema. Our data suggest that increased production of IL-13 by neonatal CD4(+) T cells is a useful marker of newborns at high risk for subsequent development of atopic diseases and that an intrinsic abnormality of CD4(+) T cell is associated with the pathogeneses of atopic disease, especially atopic dermatitis in infants.     

Granulocytic stem cell (CFUc) proliferation in experimental group B streptococcal sepsis

Adult rats infected with group B streptococci (GBS) develop neutrophilia and display a marked increase in granulocytic stem cells (CFUc). In contrast, infected neonatal rats develop a profound neutropenia and their CFUc do not increase. In order to better understand this phenomenon, we assessed the CFUc proliferative rate in control and infected adult and neonatal rats using the technique of [3H]-thymidine suicide. Beginning only 3 h after GBS inoculation, adult rats increased CFUc proliferative activity, as illustrated by an increase in thymidine suicide, from 38 +/- 2% cell kill in control animals to 70 +/- 2% when infected (mean + S.E., P less than 0.001). In contrast, the CFUc thymidine suicide rate did not increase in infected neonates. It was noted, however, that the baseline CFUc thymidine suicide rate in uninfected neonatal rats exceeded the rate in uninfected adult rats by 2-3-fold. The CFUc thymidine suicide rate was therefore determined in uninfected premature (74 +/- 1%), newborn (70 +/- 2%), 1-wk-old (70 +/- 1%), 6-wk-old (32 +/- 1%) and 6-month-old (37 +/- 3%) rats. These findings suggest that the proliferative rate of granulocytic stem cells is already maximal or near maximal in noninfected neonatal animals. In contrast to adults, the neonates' granulocyte production from stem cells can not significantly increase, even if bacterial infection is present.     

Genetic variants of TNF-[FC12]a,IL-1beta,IL-4 receptor [FC12]a-chain,IL-6 and IL-10 genes are not risk factors for sepsis in low-birth-weight infants

The amount of inflammatory cytokines is a major determinant for the development of sepsis in very-low-birth-weight (VLBW) neonates. We investigated whether variants of tumor necrosis factor-alpha, interleukin (IL)-1 beta, IL-4 receptor alpha-chain, IL-6 and IL-10 genes, associated with altered cytokine production, might influence the risk and complications of sepsis in VLBW infants. We determined the presence of these genetic variants in dried blood samples of 33 septic, 35 infected and 35 healthy VLBW neonates by PCR and RFLP methods and analyzed their association with the risk and complications of sepsis. The frequencies of genetic variants did not differ in uninfected and in infected infants with or without sepsis. Moreover, none of the studied complications was associated with carrier state of any of genetic variants. Four of the 5 septic neonates with disseminated intravascular coagulation, however, carried simultaneously the variants of IL-1 beta and IL-10 genes. We concluded that these genetic polymorphisms do not influence the risk and course of sepsis in VLBW neonates.     

Cytokine inhibitors for sepsis and septic shock

Lipopolysaccharide and other bacterial products stimulate the immune cells of the host to elicit secondary inflammatory mediators, including cytokines. The 2 primary proinflammatory cytokines elicited in septic shock are tumor necrosis factor (TNF) and interleukin-1 (IL-1). Because of the importance of these cytokines in the biologic response to sepsis, they stand out as potential targets for adjunctive therapies of sepsis. This review focuses on therapies designed to inhibit the responses of TNF and IL-1, including studies in animals and humans evaluating TNF monoclonal antibodies, TNF receptor fusion proteins, IL-1 receptor antagonists, IL-1 receptor antibodies, and phosphodiesterase inhibitors. In general, the human trials have been disappointing in comparison with corresponding animal studies. As of yet, no cytokine inhibitor therapy that significantly decreases mortality in patients with severe sepsis or septic shock has been found. Copyright © 2001 by W.B. Saunders Company     

Reduced IL-10 production and -receptor expression in neonatal T lymphocytes

AIM: To further evaluate the underlying mechanism of a formerly demonstrated immature anti-inflammatory response in neonates (1). METHODS: Interleukin (IL)-10 production was measured by enzyme-linked immunosorbent-assay (ELISA) after anti-CD3/anti-CD28 costimulation of neonatal and adult T cells. IL-10 receptor expression on T lymphocytes, B lymphocytes and monocytes were analysed by flow cytometry in neonates and adult controls. RESULTS: After anti-CD3/anti-CD28 costimulation, IL-10 production of neonatal T lymphocytes was profoundly reduced (median 247 pg/mL vs. 1062 pg/mL, p < 0.0001). IL-10 receptor expression was diminished on neonatal T lymphocytes compared to adults (3% vs. 39.5% IL-10 receptor positive lymphocytes; p < 0.0001). On neonatal B lymphocytes and monocytes the IL-10 receptor expression was comparable to adult controls. CONCLUSION: The strongly reduced IL-10 receptor expression on the main immune regulative T lymphocytes in conjunction with a significantly impaired synthesis of IL-10 may play a crucial role in the formerly demonstrated deficient anti-inflammatory immune response in neonates.     

Cyclooxygenase-2 activity following traumatic brain injury in the developing rat

Cyclooxygenase (COX) is the rate-limiting enzyme in the production of prostaglandins. COX-2, the predominant COX isoform in brain, is induced by synaptic activity. COX-2-generated prostaglandins are important regulators for a range of activities under physiologic conditions. However, under pathologic conditions, COX-2 activity can produce reactive oxygen species and toxic prostaglandin metabolites that can exacerbate brain injury. In this study, we examine the developmental production of COX-2 and test the ability of a COX-2 inhibitor, SC58125, to attenuate traumatic brain injury in developing rats. We show that constitutive COX-2 concentration is low (0.5-fold adult concentration) during the first postnatal week and then increases to 3-fold of adult levels between days 14-60. Controlled cortical impact (CCI) at postnatal day (PND) 17, but not PND 7, caused an additional 3-fold increase in COX-2 content and was associated with an increase in the COX-2 product PGE2. Treatment with the COX-2 inhibitor SC58125 in PND17 rats exposed to CCI attenuated the rise in PGE2 but did not attenuate lesion volume or improve performance in the Morris water maze.     

Interleukin-11 levels in healthy and thrombocytopenic neonates

Thrombocytopenia is common in sick neonates, and affected neonates have adverse outcomes compared with those without thrombocytopenia. As impaired platelet production underlies many neonatal thrombocytopenias, affected neonates are potential candidates for hemopoietic growth factor therapy. Although recombinant human (rh) thrombopoietin remains under therapeutic development, rhIL-11, which stimulates megakaryocytopoiesis and increases platelet counts after chemotherapy, is already licensed for clinical use. However, nothing is known about IL-11 in neonates. We therefore measured plasma IL-11 by ELISA in healthy term neonates, stable preterm neonates with or without thrombocytopenia, and preterm neonates with sepsis or necrotizing enterocolitis (NEC) with or without thrombocytopenia. At birth IL-11 was undetectable (<10 pg/mL) in healthy term neonates (n = 20) and 27 of 31 (87%) stable preterm neonates. Three stable preterm neonates with detectable IL-11 (mean+/-SD, 11.3 +/- 0.4 pg/mL; median, 11.6 pg/mL) suffered chorioamnionitis, the remaining neonate (IL-11, 14 pg/mL) being one of nine with early onset thrombocytopenia (present by <72 h of age). IL-11 was also measured in 58 preterm neonates with suspected sepsis or NEC. In 25 of 58, sepsis or NEC was unconfirmed and IL-11 was undetectable. By contrast, 14 of 33 with proven sepsis or NEC had elevated IL-11 (median, 14.9 pg/mL; range, 11.2-92.2 pg/mL). Of these 33 neonates, 19 developed thrombocytopenia: nine of 19 (47%) had detectable IL-11 and 10 of 19 (53%) did not (p > 0.05). Although its role in platelet production in neonates remains unclear, these data suggest that IL-11 is involved in the endogenous cytokine response to sepsis or NEC in preterm neonates. Further studies of IL-11 in neonates are warranted to assess its role both in platelet production and in mediation of the endogenous inflammatory response.     

新生儿败血症及败血症休克时血清IL-6、IL-6mRNA表达水平的研究

为探讨血清IL－6水平变化在新生儿败血症中的意义，采用酶免疫吸附法（ELISA）检测正常与严重感染新生儿血清IL－6值，用逆转录聚合酶链反应（RT－PCR）技术测定外周血单个核细胞（PBMC）IL－6mRNA表达情况。结果：血清IL－6水平以败血症休克组最高，败血症组次之，恢复期迅速下降，检测5例败血症新生儿PBMC均见IL－6mRNA表达，而6例对照新生儿中仅3例有IL－6mRNA表达；按百分位数法初步确定血清IL－6≥23ng/L为诊断新生儿血症的参考指标，此批标敏感性为81％，特异性为83％。提示新生儿败血及败血症休克早期血清IL－6水平升高，IL－6mRNA表达增强，与病情，预后有关，早期检测意义较大。     

高迁移率族蛋白1在新生儿败血症中的表达与机制

目的 探讨高迁移率族蛋白1（HMGB1）在新生儿败血症中的表达与机制。方法 选取62例新生儿败血症患儿为败血症组,66例局部感染新生儿为局部感染组,70例健康新生儿为健康对照组。检测三组新生儿血清中IL-6、IL-8、IL-17、IL-23、C反应蛋白（CRP）和降钙素原（PCT）的含量,外周血单个核细胞中HMGB1、Toll样受体4（TLR4）、核转录因子κB（NF-κB）mRNA及TLR4、NF-κB蛋白的表达。将健康新生儿的外周血单个核细胞分为对照组、HMGB1处理组、HMGB1+TAK-242（TLR4抑制剂）组、HMGB1+PDTC（NF-κB抑制剂）组,检测各组TLR4、NF-κB、IL-8 mRNA及TLR4、NF-κB蛋白的表达。将健康新生儿的外周血单个核细胞分为对照组、LPS处理组、LPS+甘草甜素（HMGB1抑制剂）组,检测HMGB1、TLR4、NF-κB、IL-8 mRNA及TLR4、NF-κB蛋白的表达。结果 败血症组患儿血清中IL-6、IL-8、IL-17、IL-23、CRP、PCT含量均显著高于局部感染组和健康对照组（P < 0.05）。败血症组患儿外周血单个核细胞中HMGB1、TLR4、NF-κBmRNA及TLR4、NF-κB蛋白的相对表达量均显著高于局部感染组和健康对照组（P < 0.05）。HMGB1可以显著诱导外周血单个核细胞高表达TLR4、NF-κB mRNA及其蛋白（P < 0.05）;使用TAK-242可抑制TLR4、NF-κBmRNA及其蛋白的高表达,并进而抑制IL-8 mRNA的表达（P < 0.05）;使用PDTC可抑制NF-κB mRNA及其蛋白的高表达,并进而抑制IL-8 mRNA的表达（P < 0.05）。LPS可显著诱导HMGB1 mRNA,以及TLR4、NF-κBmRNA及其蛋白的高表达,进而刺激IL-8 mRNA的表达（P < 0.05）;使用甘草甜素可抑制HMGB1 mRNA的高表达,抑制TLR4、NF-κB mRNA及其蛋白的高表达,进而降低IL-8 mRNA的高表达（P < 0.05）。结论 HMGB1可能通过激活TLR4/NF-κB信号通路诱导IL-8等炎症因子的高分泌在新生儿败血症的发病中起重要作用,HMGB1阻断剂甘草甜素可抑制TLR4/NF-κB信号通路的活化及炎症因子的分泌。     

Effects of sepsis on neonatal thrombopoiesis

We serially evaluated the effects of sepsis and/or necrotizing enterocolitis (NEC) on neonatal thrombopoiesis, using a panel of tests that included platelet counts, thrombopoietin concentrations (Tpo), circulating megakaryocyte progenitor concentrations (CMPs), and reticulated platelets (RPs). Variables analyzed included sepsis type, time after onset of sepsis, platelet counts, and gestational (GA) and postconceptional ages (PCA). Twenty neonates were enrolled. Ten had Gram-negative, six had Gram-positive, and four had presumed sepsis. Four neonates had NEC stage II or higher, and six developed thrombocytopenia. Overall, septic neonates had significantly elevated Tpo concentrations and circulating megakaryocyte progenitors. The highest Tpo levels were associated with Gram-negative or presumed sepsis. RP percentages were increased only in neonates with low platelet counts, while RP counts (RP% x platelet count) were elevated in neonates with high platelet counts. Our findings suggest that septic neonates up-regulate Tpo production, leading to increased megakaryocytopoiesis and platelet release, although the degree of upregulation is moderate. The changes in RP% and RP count most likely reflect increased thrombopoiesis with variable degrees of platelet consumption. In addition, our findings suggest that different factors, likely including level of illness and/or specific platelet or bacterial products, can down-regulate the magnitude of the thrombopoietic response.     

In vivo effect of recombinant human granulocyte colony-stimulating factor on neutrophilic expression of CD11b in septic neonates: a randomized controlled trial

Neonates are susceptible to septicemia secondary to quantitative and qualitative neutrophilic defects. Granulocyte colony-stimulating factor (G-CSF) stimulates myeloid progenitor cell proliferation and induces selective neutrophil functions. The authors aimed to evaluate the effect of G-CSF administration in septic neonates on neutrophil production and CD11b expression. Sixty septic neonates were randomized to receive intravenous G-CSF 10 μg/kg/day for 3 days (G-CSF group, n = 30), or not to receive G-CSF (non-G-CSF group, n = 30). Thirty healthy newborns were included as controls. Laboratory investigations included complete blood count, C-reactive protein, blood culture, renal and liver function tests, and assessment of neutrophilic expression of CD11b. Total leukocytes count (TLC), absolute neutrophil count (ANC), and immature myeloid cell count in G-CSF group showed significant difference between post-and pre-G-CSF levels. TLC, ANC, immature myeloid cell count and immature/total myeloid cells ratio were higher in G-CSF group compared to non-G-CSF group on days 1 and 3. Higher neutrophilic expression of CD11b was reported in both septic groups on day 0 compared to control group. On day 5, CD11b was higher in G-CSF group than non-G-CSF group. G-CSF improved CD11b% in neutropenic and non-neutropenic septic neonates. No significant difference was found between pre- and posttreatment renal and liver function tests. Lower duration of antibiotic intake and hospitalization was observed in G-CSF group compared to non-G-CSF group. G-CSF administration as an adjuvant therapy for neonatal septicemia, whether neutropenic or not, improves neutrophilic count and function and contributed to early healing from sepsis.     

Purified neonatal plasmacytoid dendritic cells overcome intrinsic maturation defect with TLR agonist stimulation

Neonates are more susceptible than adults to viral and bacterial diseases. We hypothesized that plasmacytoid dendritic cells, the cells that provide large amounts of IFN-alpha in response to Toll-like receptor 9 (TLR9) agonists, are defective in neonates. To assess the intrinsic functionality of plasmacytoid dendritic cells from neonates we compared IFN-alpha production by plasmacytoid dendritic cells derived from neonates versus adults in both whole blood and in purified plasmacytoid dendritic cells. TLR9-stimulation of whole blood from adults and neonates resulted in comparable amounts of IFN-alpha production. However, we observed small but significant differences in IFN-alpha production from purified CD123+ plasmacytoid dendritic cells from neonates after stimulation with the TLR9 ligand CpG-DNA. Furthermore, we assessed surface expression of co-stimulatory molecules on plasmacytoid dendritic cells after stimulation. While purified CD123+ plasmacytoid dendritic cells from adults up-regulated co-stimulatory molecules CD80 and CD86 with IL-3 alone those from neonates required the addition of CpG-DNA to reach adult levels. Therefore, the intrinsic deficiencies of neonatal plasmacytoid dendritic cells can be mitigated by TLR9 agonists. These results are consistent with the observation that vaccines that effect strong adjuvant activity on dendritic cells can induce protective responses in neonates.     

超声心输出量监护仪监测脓毒症新生儿心功能的研究

目的 使用便携式超声心输出量监护仪(ultrasonic cardiac output monitor,USCOM)监测脓毒症新生儿的心功能变化.方法 使用USCOM测量32例轻度脓毒症新生儿、19例重度脓毒症新生儿及33例健康新生儿(对照组)心功能相关指标,比较3组心功能差异及所有脓毒症新生儿给予改善心功能治疗前后心功能变化的差异.结果 轻度脓毒症组、重度脓毒症组与对照组相比,心率、外周血管阻力高于对照组,心脏指数、心输出量、每搏输出量、主动脉峰流速低于对照组,差异有统计学意义(P<0.05).重度脓毒症组患儿心脏指数、心输出量、每搏输出量低于轻度脓毒症组患儿,差异有统计学意义(P<0.05).所有脓毒症患儿改善心功能治疗后心功能相关指标较治疗前改善,差异有统计学意义(P<0.05).结论 脓毒症新生儿存在早期心功能变化,使用USCOM可快速、简便、动态了解脓毒症新生儿的心功能及整体循环状态,为治疗及评估病情提供依据.     

Dysregulation of expression of immunoregulatory and cytokine genes and its association with the immaturity in neonatal phagocytic and cellular immunity

BACKGROUND: Innate and adaptive immunity is comprised of cellular and humoral factors that provide rapid protection against microbial invasion. However, immaturity of innate and adaptive immune responses in the perinatal period predisposes the neonate to increased infectious morbidity and mortality from a variety of organisms. OBJECTIVES: To elucidate dysregulation of expression of various immunoregulatory and cytokine genes and its association with the immaturity in neonatal phagocytic cellular immunity. METHODS: Comparison of protein production and mRNA of granulocyte macrophage colony-stimulating factor (GM-CSF), macrophage colony-stimulating factor (M-CSF), granulocyte colony-stimulating factor (G-CSF), interleukin (IL)-12, IL-15 and IL-18 in adult peripheral blood (APB) mononuclear cells (MNC) and cord blood (CB) MNC was studied. Effects of hematopoietic growth factors (HGFs, GM-CSF, M-CSF, G-CSF, IL-11) were studied in vivo in rats as well as randomized controlled studies conducted in neonates. Oligonucleotide microarrays were used to study gene expression patterns of activated CB and APB monocytes and dendritic cells. RESULTS AND CONCLUSIONS: We demonstrated dysregulation of various immunoregulatory and cytokine genes in CB MNC. This dysregulation may in part explain the immaturity of neonatal cell-mediated immunity. There are probably various dysregulated cytokines yet to be discovered. Biological agents such as IL-2, IL-12, IL-11 and/or IL-18 alone or in combination with HGFs should be considered for future studies to identify new approaches to enhance neonatal host defense, and thereby decrease the incidence of neonatal sepsis and the consequent high risk of morbidity and mortality.     

Experimental neonatal syphilis. II. Immunological responses of neonatal rabbits to intradermal inoculation with Treponema pallidum (Nichols strain)

The immunological competence of neonatal rabbits inoculated intradermally with Treponema pallidum was examined. Both cellular responses and the production of humoral antibody to specific T. pallidum antigens and to nonspecific antigens or mitogens were investigated. In blast transformation assays, splenic and popliteal lymph node lymphocytes from neonates inoculated with virulent T. pallidum responded to T. pallidum antigens in a manner similar to or greater than inoculated adult rabbits. Splenic and popliteal lymph node lymphocytes from both uninoculated and T. pallidum-inoculated neonate and adult animals showed consistent and similar responses to concanavalin A. Both neonate and adult animals inoculated with heat-killed T. pallidum also responded but to a significantly lesser degree. Immunofluorescent examination of skin sections from the site of inoculation of adult and neonatal animals revealed 1) that the early infiltrate was composed predominantly of T cells, 2) diffuse antibody staining with rare B cells, and 3) fewer treponemes with significant fragmentation in neonates as compared to adult controls. Antibody production by neonates inoculated with virulent T. pallidum was delayed 4 to 6 weeks postinoculation as measured by the fluorescent Treponemal antibody absorption and Venereal Disease Research Laboratory (VDRL) test procedures, respectively. Antibody was not detected among neonates inoculated with heat-killed treponemes during a 6-week observation period and only low levels of VDRL antibody were detected in a few adult control animals. Evidence for incomplete resistance of neonatal rabbits to the intradermal inoculation of Treponema pallidum was provided.(ABSTRACT TRUNCATED AT 250 WORDS)