interleukin-8 and Hypoxia-Ischemia--Brain

Topics: Case-Control Studies; Enzyme-Linked Immunosorbent Assay; Female; Humans; Hypoxia-Ischemia, Brain; Infant, Newborn; Intercellular Adhesion Molecule-1; Interleukin-8; Male; Matrix Metalloproteinase 2; Polymorphism, Genetic; Severity of Illness Index; Tumor Necrosis Factor-alpha

We aimed to assess whether a gene expression assay provided insights for understanding the heterogeneity among newborns affected by neonatal encephalopathy (NE).. Analysis by RT-qPCR of the mRNA expression of candidate genes in whole blood from controls (n = 34) and NE (n = 24) patients at <6, 12, 24, 48, 72 and 96 h of life, followed by determination of differences in gene expression between conditions and correlation with clinical variables.. During the first 4 days of life, MMP9, PPARG, IL8, HSPA1A and TLR8 were more expressed and CCR5 less expressed in NE patients compared to controls. MMP9 and PPARG increased and CCR5 decreased in moderate/severe NE patients compared to mild. At 6-12 h of life, increased IL8 correlated with severe NE and death, decreased CCR5 correlated with chorioamnionitis and increased HSPA1A correlated with expanded multiorgan dysfunction, severe NE and female sex.. MMP9, PPARG and CCR5 mRNA expression within first days of life correlates with the severity of NE. At 6-12 h, IL8 and HSPA1A are good reporters of clinical variables in NE patients. HSPA1A may have a role in the sexual dimorphism observed in NE. CCR5 is potentially involved in the link between severe NE and chorioamnionitis.

Topics: Chorioamnionitis; Female; Gene Expression Profiling; Gene Expression Regulation; HSP70 Heat-Shock Proteins; Humans; Hypothermia, Induced; Hypoxia-Ischemia, Brain; Hypoxia, Brain; Infant, Newborn; Infant, Newborn, Diseases; Interleukin-8; Male; Matrix Metalloproteinase 9; PPAR gamma; Pregnancy; Prospective Studies; Receptors, CCR5; RNA, Messenger; Sex Factors; Toll-Like Receptor 8

In a clinical trial of cerebral palsy, the level of plasma interleukin-8 (IL-8) was increased, correlated with motor improvement, after human umbilical cord blood mononuclear cell (hUCBC) infusion. This study aimed to elucidate the role of IL-8 in the therapeutic effects of hUCBCs in a mouse model of hypoxic-ischaemic brain injury (HI). In P7 HI mouse brains, hUCBC administration at day 7 after HI upregulated the gene expression of Cxcl2, the mouse IL-8 homologue and increased the expression of its receptor, CXCR2. hUCBC administration restored the sequential downstream signalling axis of p-p38/p-MAPKAPK2, NFκB, and angiogenic factors, which were downregulated by HI. An in vitro assay revealed the downregulation of the angiogenic pathway by CXCR2 knockdown and p38 inhibition. In vivo p38 inhibition prior to hUCBC administration in HI mouse brains produced identical results. Behavioural outcomes revealed a therapeutic effect (ps < 0.01) of hUCBC or IL-8 administration, which was correlated with decreases in infarct size and angiogenic findings in the striatum. In conclusion, the response of the host to hUCBC administration in mice upregulated Cxcl2, which led to the activation of the IL-8-mediated p-p38 signalling pathway. The upregulation of the downstream pathway and angiogenic growth factors via NFκB can be inferred to be the potential therapeutic mechanism of hUCBCs.

Topics: Animals; Animals, Newborn; Brain Injuries; Cells, Cultured; Cord Blood Stem Cell Transplantation; Disease Models, Animal; Human Umbilical Vein Endothelial Cells; Humans; Hypoxia-Ischemia, Brain; Intercellular Signaling Peptides and Proteins; Interleukin-8; Leukocytes, Mononuclear; Mice; Neovascularization, Physiologic

Hypothermia with xenon gas has been used to reduce brain injury and disability rate after perinatal hypoxia-ischemia. We evaluated xenon gas therapy effects in an in vitro model with or without hypothermia on cultured human airway epithelial cells (Calu-3).. Calu-3 monolayers were grown at an air-liquid interface and exposed to one of the following conditions: 1) 21% FiO2 at 37°C (control); 2) 45% FiO2 and 50% xenon at 37°C; 3) 21% FiO2 and 50% xenon at 32°C; 4) 45% FiO2 and 50% xenon at 32°C for 24 hours. Transepithelial resistance (TER) measurements were performed and apical surface fluids were collected and assayed for total protein, IL-6, and IL-8. Three monolayers were used for immunofluorescence localization of zonula occludens-1 (ZO-1). The data were analyzed by one-way ANOVA.. TER decreased at 24 hours in all treatment groups. Xenon with hyperoxia and hypothermia resulted in greatest decrease in TER compared with other groups. Immunofluorescence localization of ZO-1 (XY) showed reduced density of ZO-1 rings and incomplete ring-like staining in the 45% FiO2- 50% xenon group at 32°C compared with other groups. Secretion of total protein was not different among groups. Secretion of IL-6 in 21% FiO2 with xenon group at 32°C was less than that of the control group. The secretion of IL-8 in 45% FiO2 with xenon at 32°C was greater than that of other groups.. Hyperoxia and hypothermia result in detrimental epithelial cell function and inflammation over 24-hour exposure. Xenon gas did not affect cell function or reduce inflammation.

Topics: Anesthetics, Inhalation; Cells, Cultured; Humans; Hyperoxia; Hypothermia; Hypoxia-Ischemia, Brain; Inflammation; Inflammation Mediators; Interleukin-6; Interleukin-8; Respiratory Mucosa; Tight Junctions; Treatment Outcome; Xenon

MSCs are a promising therapeutic resource. Paracrine effects and the induction of differentiation patterns are thought to represent the two primary mechanisms underlying the therapeutic effects of mesenchymal stem cell (MSC) transplantation in vivo. However, it is unclear which mechanism is involved in the therapeutic effects of human umbilical cord-derived MSC (hUC-MSC) transplantation.. Based on flow cytometry analysis, hUC-MSCs exhibited the morphological characteristics and surface markers of MSCs. Following directed neural induction, these cells displayed a neuron-like morphology and expressed high levels of neural markers. All types of hUC-MSCs, including differentiated and redifferentiated cells, promoted learning and memory function recovery in hypoxic-ischemic brain damaged (HIBD) rats. The hUC-MSCs secreted IL-8, which enhanced angiogenesis in the hippocampus via the JNK pathway. However, the differentiated and redifferentiated cells did not exert significantly greater therapeutic effects than the undifferentiated hUC-MSCs.. hUC-MSCs display the biological properties and neural differentiation potential of MSCs and provide therapeutic advantages by secreting IL-8, which participates in angiogenesis in the rat HIBD model. These data suggest that hUC-MSC transplantation improves the recovery of neuronal function via an IL-8-mediated secretion mechanism, whereas differentiation pattern induction was limited.

Topics: Animals; Biomarkers; Cell Differentiation; Cells, Cultured; Hippocampus; Humans; Hypoxia-Ischemia, Brain; Interleukin-8; Learning; Memory; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells; Neovascularization, Pathologic; Neurons; Rats; Rats, Sprague-Dawley; Umbilical Cord

We investigated changes in the levels of significant cytokines in relation to neonatal seizures, a pattern of cytokine concentrations serially and the severity of brain insult. The hypoxic-ischaemic encephalopathy-induced seizure group consisted of 13 patients, and another 15 normal newborns were enrolled as a control group. All of the initial samples were obtained within the first 24 h of admission, and the second samples were obtained between 48 and 72 h in both groups. Only the third samples were taken in the seizure group on the 5th day. During neonatal seizures, the levels of most cytokines increased within 24 h, and, in particular, the levels of interleukin (IL)-8 significantly increased (P < 0.05). After 48-72 h of seizure onset, the levels of most cytokines decreased, especially, IL-1Ra; however, IL-8 and IL-10 remained increased (P < 0.05). During the prognosis, one patient who was diagnosed with quadriplegic cerebral palsy at 6 months of age presented extreme elevation of IL-1beta, IL-1Ra, IL-6, IL-8, IL-10 and tumor necrosis factor-alpha in the initial sample, reflecting the severity of brain damage. A significant increase in IL-8 may serve as a biomarker for earlier detection of brain damage in neonatal seizure, if detected within 24 and 48-72 h of the seizure.

Topics: Biomarkers; Enzyme-Linked Immunosorbent Assay; Female; Humans; Hypoxia-Ischemia, Brain; Infant, Newborn; Interleukin 1 Receptor Antagonist Protein; Interleukin-10; Interleukin-8; Male; Seizures

To explore whether or not the umbilical blood levels of cytokines can be used to indicate the adverse outcomes of hypoxic-ischemic encephalopathy (HIE) patients. Umbilical artery blood and peripheral venous blood samples were collected on the 1st, 3rd and 7th days after birth to detect the levels of IL-1 beta, IL-8 and TNF-alpha. Neurological examination and Denver developmental screening test (DDST-II) were performed at the 6 and 12 months evaluations to detect any neurodevelopmental abnormalities. The results showed: (i) the serum concentrations of IL-1 beta, IL-8 and TNF-alpha in umbilical and peripheral blood were significantly higher in HIE patients than control groups; (ii) the umbilical blood concentrations of IL-1 beta exhibited the best positive correlation with HIE grades, when compared with IL-8 and TNF-alpha; and (iii) abnormal neurological outcomes at 6 and 12 months of age were best predicted by umbilical levels of IL-1 beta. Thus, umbilical concentrations of IL-1 beta were associated with the grades and adverse outcomes of HIE.

Topics: Adult; Asphyxia Neonatorum; Case-Control Studies; Female; Fetal Blood; Humans; Hypoxia-Ischemia, Brain; Infant, Newborn; Interleukin-1beta; Interleukin-8; Male; Neurologic Examination; Pregnancy; Reference Values; Severity of Illness Index; Treatment Outcome; Tumor Necrosis Factor-alpha; Umbilical Cord