Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0029713 (immaturity)
 4,335 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The cytokine interleukin-1 (IL-1) is a potent activator of the hypothalamic-pituitary-adrenal (HPA) axis. During postnatal development, the rat appears to be hyporesponsive to many stimuli which activate the HPA system in adulthood. Since hyporesponsiveness depends to a large extent on the stimulus, these experiments investigated the ontogeny of the HPA axis and interleukin-6 (IL-6) responses to IL-1 beta. Six-, 9-, and 18-day-old pups were injected with human recombinant IL-1 beta and plasma ACTH, corticosterone (CORT) and IL-6 levels were measured. IL-1 beta administration resulted in age-dependent endocrine and immune responses. The younger neonates secreted less ACTH and CORT and more IL-6. This was not due to a lowered capacity of the pituitary to synthesize and secrete ACTH since peptide levels following adrenalectomy did not reveal age differences. These data suggest that the diminished response to IL-1 beta is due to the immaturity of neural circuits which may be required to fully activate the HPA axis to immune signals.
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PMID:Pituitary-adrenal and interleukin-6 responses to recombinant interleukin-1 in neonatal rats. 819 Aug 34

The cellular immune system of the newborn infant is immature and hypo-responsive when compared with adults. The extent to which immaturity of the leucocyte function underlies hyporesponsiveness in the newborn is incompletely understood. In this study flow cytometric techniques were applied to investigate the concurrent expression of a range of surface and intracellular leucocyte functional molecules and cytokines in resting and stimulated cord and adult blood. Production of interleukin (IL)-2 and expression of the components of its receptor, IL-2R alpha/beta/gamma, were investigated. No differences in the proportion of leucocytes producing IL-2R alpha and IL-2R gamma were observed for newborns and adults. A lower proportion of T cells and natural killer (NK) cells from newborns expressed IL-2R beta and upregulation of expression was slower. We hypothesize that reduced IL-2R beta may curtail early autocrine IL-2 activation of immune responses in the newborn. This hypothesis was supported by the observation that an increased proportion of stimulated T cells from newborns produced IL-2 at 4 h poststimulation, but at 24 h the proportion was lower than for adult T cells. The very low levels of interferon (IFN)-gamma produced by neonatal T cells and NK cells may also be partly explained by a curtailment of early autocrine activation of T cells. Expression and kinetics of upregulation for other functional molecules were studied. CD71, HLA-DR, tissue factor and CD152 levels were not significantly different for adults and newborns, suggesting that cord blood leucocytes, in some respects, may demonstrate functional maturity. IL-6 secretion by stimulated monocytes was also comparable in cord and adult blood. However, IL-1 alpha and IL-1 beta were produced by a lower proportion of monocytes from newborns than adults. Similarly, tumour necrosis factor (TNF)-alpha production for monocytes and T cells was lower in cord blood. The mean fluorescence intensity for IL-1 alpha, IL-1 beta and TNF-alpha was also lower for leucocytes from cord blood. These findings are significant in relation to the inability of newborn infants to mount a febrile response to infection. The findings of lower expression of IL-2R beta and lower production of inflammatory cytokines IL-1 alpha, IL-1 beta and TNF-alpha is a basis for improved understanding of the immunological immaturity of leucocytes in the newborn.
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PMID:Cord blood leucocyte expression of functionally significant molecules involved in the regulation of cellular immunity. 1116 9

Cord blood (CB) transplantations are associated with low graft-versus-host disease (GVHD). The pathophysiology of GVHD involves interaction and activation of different cell types, as lymphocytes and monocytes, and results in a cascade of cytokine production. After antigen or mitogen stimulation, CB monocytes release lower levels of cytokines than adult blood (AB) monocytes. In this study, the detection of intracellular IL-1 beta and TNF-alpha produced by monocytes was evaluated in response to tuberculin PPD to investigate whether the reduced capacity of CB monocytes to secrete cytokines could be related to an impaired functional activity and to a particular phenotypic profile. Results showed that the percentage of CD64(+)monocytes producing intracellular IL-1 beta and TNF-alpha was significantly lower in CB and that the phenotypic profile of CB monocytes producing these cytokine (CD64(+)CD14(+)) was different to that of AB monocytes (CD64(+)CD14(+), CD64(+)CD33(+) and CD64(+) CD45RO(+)). These results suggest that the lower capacity of CB monocyte populations to produce IL-1 beta and TNF-alpha might be due to a functional immaturity of CB monocytes at the cellular level as reflected by the different phenotypic profile of CB monocytes.
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PMID:Intracellular cytokine profile of cord and adult blood monocytes. 1143 25

Haematopoietic stem cell transplantation is indicated in several haematologic and genetic diseases, the most notable being aplastic anemia and leukemias. Bone marrow has been the traditional source of these cells. Human umbilical cord blood (UCB) has recently become an alternative source of haematopoietic stem cells for transplants. The advantages of cord blood include noninvasive collection without risk to mother and neonate, low risk of viral infection, and immunologic immaturity of cord cells. Single umbilical cord blood donation is usually sufficient for transplantation to adult recipients. Additionally, banking of HLA-typed UCB appears valuable in patients lacking a family donor. This study has focused on basic "perinatological" parameters of umbilical cord blood: average volume of single donation UCB and initial storage conditions before isolation of haematopoietic stem cells. Additionally, the mean content of CD34+ haematopoietic stem cells in leukocyte, lymphocyte and mononuclear cell fractions was established. Correlations between levels of so-called pro-inflammatory cytokines (present in cord blood serum) and number, viability and clonogenicity of cord blood mononuclear cells were checked. UCB samples were obtained by "open" collection during vaginal deliveries and cesarean sections. The collected blood was stored in solutions of anticoagulants (ACD, CPDA-1, heparin) and culture media (PBS, Iscove medium, RPMI), during several time intervals (0-1 h, 1-6 h, 6-12 h, 12-24 h) and at two temperatures (+4 degrees C, ambient). UCB volumes, as well as MNC counts, correlated with delivery type, placental weight, neonatal body weight and duration of pregnancy. The concentration, viability and clonogenicity of MNCs were assessed after collection and storage. The subpopulation of CD34+ haematopoietic stem cells was isolated from MNCs using monoclonal antibodies and magnetic-based separation. The number, viability and clonogenicity of CD34+ cells were evaluated. Subsequently in some samples, the concentration of proinflammatory cytokines (IL-1 alpha, IL-1 beta, IL-6, IL-8, and TNF-alpha), number of mononuclear cells and in vitro clonogenicity of myeloid progenitors (CFU-GM) were determined. It was found that the collected blood volume depended on neonatal body weight (Fig. 1). Umbilical blood could be stored either at ambient temperature (Fig. 4) or +4 degrees C (recommended because of reduced risk of infection) for up to 24 hours in RPMI solution (Fig. 5) with heparin (Fig. 2, 3). CD34+ cell count correlated with mononuclear cell count only (Fig. 6). A negative correlation between the number of mononuclear cells and concentration of TNF-alpha was revealed (Fig. 7), as well as between the number of detectable CFU-GM and concentration of IL-1 beta (Fig. 8). In conclusion, UCB collection and short-term storage is a safe and simple method for graftable haematopoietic stem cell recovery. Save for IL-1 beta and TNF-alpha, cytokine levels did not correlate with the studied parameters of umbilical cord blood.
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PMID:[Improved method for delivery room collection and storage of human cord blood cells for grafting]. 1251 5

Due to developmental immaturity of the central nervous system, effects of an adverse intrauterine environment and need for intensive care postnatally, preterm infants are at high risk of sustaining brain injury in the perinatal period. Infants who suffer brain injury in the perinatal period are at risk for long-term neurodevelopmental sequelae. Clinical and experimental data supports a significant role for inflammatory mediators in the pathophysiology of perinatal brain injury. Abnormalities in coagulation proteins in the sick preterm newborn may accentuate the risk for intraventricular hemorrhage. Polymorphisms in TNF alpha , IL-1 beta , IL-4, IL-6 and IL-10 as well as mutations in coagulation proteins have been investigated as potential candidate genes to modify risk and or severity of perinatal brain injury. Preliminary evidence suggests a role for cytokine genes as risk modifiers for IVH and PVL.
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PMID:Genetics of perinatal brain injury in the preterm infant. 1636 23

Exposure of human skin to solar ultraviolet (UV) light induces local and systemic immune suppression. It is known that alterations of immune functions of Langerhans cells (LCs) and dermal dendritic cells (DDCs) mediate this phenomenon. The purpose of this study was to mimic in vitro the early UV-induced skin disruption to better understand the involvement of the skin micro-environment in triggering this immunosuppressive state. We therefore developed skin equivalents (SEs) integrating LCs and DDCs derived from monocytes (mo-LCs and mo-DDCs, respectively). First, we showed that Langerin(+) mo-LC and dendritic cell (DC)-specific ICAM-3 grabbing nonintegrin (SIGN)(+) mo-DDCs were immunolocalized in situ in epidermal and dermal compartments of SEs, respectively. The SE micro-environment without immune cells displayed full cytokine profile that may ensure and maintain differentiation, localization, and immaturity of LCs and DDCs in situ, as shown by secretion of granulocyte-macrophage colony-stimulating factor, transforming growth factor beta (beta)-1, interleukin (IL)-4, IL-13, and IL-15 involved in cell differentiation; presence of complete chemokine network as macrophage inflammatory protein 3 alpha (alpha); low secretion of pro-inflammatory cytokines tumor necrosis factor alpha (TNF-alpha), IL-1 beta, IL-6, and IL-8; and surprising secretion of immunosuppresive cytokine IL-10. Second, we demonstrated that skin micro-environment homeostasis was greatly disrupted under solar UV irradiation of SEs. In fact, we showed a pro-inflammatory state characterized by high secretion of TNF-alpha, IL-1 beta, IL-6, and IL-8 and low secretion of IL-10. This breakdown of immune homeostasis was visualized at the same time as in situ migration of mo-LCs and mo-DDCs into the dermal equivalent of SEs. Moreover, this tissue migration of mo-LCs and mo-DDCs into SEs was in accordance with the chemokine (C-C motif) receptor 7 expression and the DC-lysosome-associated membrane glycoprotein acquisition only on mo-LCs. Our results highlighted major participation of the skin micro-environment in the triggering and modulating of UV-induced skin immune responses. In addition, it could be concluded that these SEs are reliable tools for modeling biological events inaccessible in humans.
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PMID:Effects of solar ultraviolet radiation on engineered human skin equivalent containing both Langerhans cells and dermal dendritic cells. 1788 23

The efficacy of the neonatal innate immune system to respond to bacterial exposure following maternal infection is of great interest, as the neonatal period is one of relative immune immaturity, and is associated with high rates of morbidity and mortality. This study aimed to determine the response to an in-vivo endotoxin challenge in the neonatal period following prenatal exposure to bacterial endotoxin. Pregnant Fischer 344 dams received either endotoxin or the vehicle on gestational days 16, 18 and 20 (term=23 days). The neonatal (5 day) offspring were then exposed to an endotoxin challenge; blood was collected at baseline or at 4 h for analysis of blood cell counts, corticosterone, TNF alpha and IL-1 beta, levels. The neonatal rat pups responded to the challenge with significantly reduced corticosterone, TNF alpha and IL-1 beta levels compared to controls (p<0.003). Monocyte, neutrophil and eosinophil counts were also significantly reduced in the prenatal endotoxin offspring compared to controls (p<0.02). While the immune system is functionally immature in the neonatal period, these results suggest that prenatal infection may further reduce the capacity of the innate neonatal immune system to respond to endotoxin, leaving offspring more vulnerable to pathogenic invasion in neonatal life.
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PMID:Innate immune dysfunction in the neonatal rat following prenatal endotoxin exposure. 1870 68