RESUMO
The structure and function of infant skin is not fully developed until 34 weeks of gestation, and this immaturity is associated with risk of late-onset sepsis (LOS). Topical coconut oil improves preterm-infant skin integrity and may reduce LOS. However, data on early-life skin-microbiome succession and potential effects of emollient skin care in preterm infants are scarce. We therefore collected skin-microbiome samples from the ear, axilla, and groin on days 1, 7, 14, and 21 from preterm infants born <30 weeks of gestation as part of a randomized clinical trial of standard skin care vs. topical coconut oil. We found that within-sample microbiome diversity was highest on day 1 after birth, with a subsequent decline and emergence of Staphylococcus genus dominance from day 7. Moreover, microbiome assembly was less diverse in infants receiving coconut oil vs. standard skin care. Our study provides novel data on preterm-infant skin-microbiome composition and highlights the modifying potential of emollient skin care.
Assuntos
Microbiota , Sepse , Lactente , Recém-Nascido , Humanos , Recém-Nascido Prematuro , Óleo de Coco/farmacologia , Emolientes/farmacologia , PeleRESUMO
OBJECTIVE: We compared mortality and morbidity of inborn versus outborn very preterm infants <32 weeks' gestation in Western Australia (WA) between 2005 and 2018. DESIGN: Retrospective cohort study. PATIENTS: Infants <32 weeks' gestation who were born in WA. MAIN OUTCOME MEASURES: Mortality was assessed as death before discharge home from the tertiary neonatal intensive care unit. Short-term morbidities included combined brain injury (intracranial haemorrhage grade ≥3 and cystic periventricular leukomalacia) and other major neonatal outcomes. Developmental assessments at age 2, 3 and 5 years were evaluated. We performed multivariable logistic regression analysis of outborn status on outcomes, controlling for gestational age, birth weight z-score, sex and multiple birth. RESULTS: A total of 4974 infants were born in WA between 22 and 32 weeks' gestation between 2005 and 2018 of which 4237 (89.6%) were inborn and 443 (10.4%) were outborn. Overall mortality to discharge was higher in outborn infants (20.5% (91/443) vs 7.4% (314/4237); adjusted OR (aOR) 2.44, 95% CI 1.60 to 3.70, p<0.001). Outborn infants had higher rates of combined brain injury than those inborn (10.7% (41/384) vs 6.0% (246/4115); aOR 1.98, 95% CI 1.37 to 2.86), p<0.001). No difference in up to 5-year developmental measures was detected. Follow-up data were available for 65% of outborn and 79% of inborn infants. CONCLUSIONS: Outborn preterm infants <32 weeks in WA had increased odds of mortality and combined brain injury than those inborn. Developmental outcomes up to 5 years were similar between groups. Loss to follow-up may have impacted the long-term comparison.
Assuntos
Lesões Encefálicas , Recém-Nascido Prematuro , Feminino , Recém-Nascido , Lactente , Humanos , Estudos de Coortes , Austrália Ocidental/epidemiologia , Mortalidade Infantil , Estudos Retrospectivos , Idade Gestacional , Lesões Encefálicas/epidemiologiaRESUMO
Pentoxifylline (PTX) is administered as 6- or 12-hour intravenous infusions in the treatment of sepsis or necrotizing enterocolitis in neonates; however, there is a paucity of formal stability data for PTX in the end-use solution. We investigated PTX stability in the simulated clinical conditions of neonatal intensive care, where PTX injection is diluted to 5 mg/mL and administered via syringe pump. A stability-indicating high performance liquid chromatography (HPLC) assay was established for PTX. The clinical simulation stability study comprised PTX 5 mg/mL in 20 mL syringes and was conducted at three temperatures, all protected from light: refrigerator (4°C); room temperature (22°C) and incubator/humidicrib (35°C). PTX stability also was evaluated at room temperature and exposed to light. Samples were drawn at pre-determined times over a 10 day period and stored frozen (-80°C) until assayed by HPLC. A single exponential equation was fitted to the concentration-time data to determine PTX stability. Forced degradation studies confirmed that PTX was stable at elevated temperature (up to 45°C), exposed to light and under acidic stress for up to 10 days, but subject to degradation under alkali and oxidative stress. PTX injection 5 mg/mL in 0.9% w/v sodium chloride or 5% w/v glucose was found to be stable when protected from light at 22°C and 35°C, and exposed to light at 22°C for at least 7 days. These data provide clinically relevant evidence that PTX injection is stable in the end-use, ICU/incubator clinical conditions for at least 24 hours.
Assuntos
Pentoxifilina , Criança , Cromatografia Líquida de Alta Pressão , Estabilidade de Medicamentos , Armazenamento de Medicamentos , Humanos , Recém-Nascido , Infusões Intravenosas , Injeções , Seringas , TemperaturaRESUMO
BACKGROUND: Late-onset sepsis (LOS) with Staphylococcus epidermidis is common in preterm infants, but the immunological mechanisms underlying heightened susceptibility are poorly understood. Our aim is to characterize the ontogeny of cytokine responses to live S. epidermidis in preterm infants with and without subsequent Gram-positive LOS. METHODS: We conducted a prospective, observational cohort study of preterm infants (<30 weeks gestational age [GA]) with blood sampling on Days 1, 7, 14, 21, and 28 of life. Cytokine responses in peripheral whole blood stimulated with live S. epidermidis were analyzed by 11-plex immunoassay. RESULTS: Of 129 infants (mean GA, 26.2 weeks; mean birth weight, 887g), 23 (17.8%) had confirmed LOS with Gram-positive organisms and 15 (11.6%) had clinical sepsis, with median onsets at 13 and 15 days, respectively. Blood cytokine responses to an in vitro S. epidermidis challenge were similar between infected and uninfected infants on Day 1, but diverged thereafter. Infants with subsequent LOS displayed broadly reduced S. epidermidis-induced responses from Day 7 onwards, compared to those who did not develop LOS. This pattern was observed with chemokines (interleukin [IL]-8, monocyte chemotactic protein-1, and macrophage inflammatory protein-1α), pro-inflammatory cytokines (IL-1, IL-6, and tumor necrosis factor-α) and the regulatory cytokine IL-10. CONCLUSIONS: Cytokine responses to a live S. epidermidis challenge are impaired in infants with LOS and precede the onset of clinical illness. Quantifying pathogen-specific cytokine responses at Day 7 may identify those high-risk preterm infants at the greatest risk of LOS, and prospective replication is warranted.
Assuntos
Citocinas/imunologia , Sepse/imunologia , Infecções Estafilocócicas/imunologia , Humanos , Lactente , Recém-Nascido , Recém-Nascido Prematuro , Estudos Prospectivos , Staphylococcus epidermidisRESUMO
Sepsis remains a leading cause of morbidity and mortality in the neonatal population, and at present, there is no unified definition of neonatal sepsis. Existing consensus sepsis definitions within paediatrics are not suited for use in the NICU and do not address sepsis in the premature population. Many neonatal research and surveillance networks have criteria for the definition of sepsis within their publications though these vary greatly and there is typically a heavy emphasis on microbiological culture. The concept of organ dysfunction as a diagnostic criterion for sepsis is rarely considered in neonatal literature, and it remains unclear how to most accurately screen neonates for organ dysfunction. Accurately defining and screening for sepsis is important for clinical management, health service design and future research. The progress made by the Sepsis-3 group provides a roadmap of how definitions and screening criteria may be developed. Similar initiatives in neonatology are likely to be more challenging and would need to account for the unique presentation of sepsis in term and premature neonates. The outputs of similar consensus work within neonatology should be twofold: a validated definition of neonatal sepsis and screening criteria to identify at-risk patients earlier in their clinical course. IMPACT: There is currently no consensus definition of neonatal sepsis and the definitions that are currently in use are varied.A consensus definition of neonatal sepsis would benefit clinicians, patients and researchers.Recent progress in adults with publication of Sepsis-3 provides guidance on how a consensus definition and screening criteria for sepsis could be produced in neonatology.We discuss common themes and potential shortcomings in sepsis definitions within neonatology.We highlight the need for a consensus definition of neonatal sepsis and the challenges that this task poses.
Assuntos
Sepse Neonatal/sangue , Sepse Neonatal/classificação , Neonatologia/normas , Biomarcadores/sangue , Consenso , Europa (Continente) , Humanos , Recém-Nascido , Recém-Nascido Prematuro , Programas de Rastreamento , Sepse Neonatal/diagnóstico , Prognóstico , Resultado do TratamentoRESUMO
BACKGROUND: Preterm infants are at high risk of infection and have distinct pathogen recognition responses. Suggested mechanisms include soluble mediators that enhance cellular levels of cAMP. The aim of this study was to assess the relationship between blood cAMP concentrations and TLR-mediated cytokine production in infants during the first month of life. METHODS: Cord and serial peripheral blood samples (days of life 1-28) were obtained from a cohort of very preterm (<30 weeks' gestational age) and term human infants. Whole-blood concentrations of cAMP and FSL-1 and LPS in vitro stimulated cytokine concentrations were measured by ELISA and multiplex bead assay. RESULTS: cAMP concentrations were higher in cord than in peripheral blood, higher in cord blood of female preterm infants, and lower at Days 1 and 7 in infants exposed to chorioamnionitis, even after adjusting for leukocyte counts. TLR2 and TLR4-mediated TNF-α, IL-1ß, IL-6, IL-12p70, and IL-10 production in vitro increased over the first month of life in preterm infants and were positively correlated with leukocyte-adjusted cAMP levels and reduced by exposure to chorioamnionitis. CONCLUSIONS: The ontogeny of blood cAMP concentrations and associations with chorioamnionitis and TLR-mediated production of cytokines suggest that this secondary messenger helps shape distinct neonatal pathogen responses in early life.
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Corioamnionite/sangue , AMP Cíclico/sangue , Citocinas/sangue , Sangue Fetal/metabolismo , Recém-Nascido Prematuro/sangue , Mediadores da Inflamação/sangue , Leucócitos/metabolismo , Receptores Toll-Like/sangue , Células Cultivadas , Corioamnionite/imunologia , Diglicerídeos/farmacologia , Feminino , Sangue Fetal/imunologia , Idade Gestacional , Humanos , Recém-Nascido , Recém-Nascido Prematuro/imunologia , Leucócitos/efeitos dos fármacos , Leucócitos/imunologia , Lipopolissacarídeos/farmacologia , Estudos Longitudinais , Masculino , Oligopeptídeos/farmacologia , Gravidez , Estudos Prospectivos , Receptores Toll-Like/agonistasAssuntos
Desenvolvimento Infantil , Óleo de Coco/administração & dosagem , Lactente Extremamente Prematuro , Nascimento Prematuro , Administração Cutânea , Fatores Etários , Pré-Escolar , Óleo de Coco/efeitos adversos , Feminino , Idade Gestacional , Humanos , Recém-Nascido , Masculino , Gravidez , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do TratamentoAssuntos
Anti-Infecciosos/sangue , Óleo de Coco/metabolismo , Lactente Extremamente Prematuro , Lauratos/sangue , Monoglicerídeos/sangue , Nascimento Prematuro , Administração Cutânea , Anti-Infecciosos/administração & dosagem , Candida albicans/efeitos dos fármacos , Candida albicans/crescimento & desenvolvimento , Óleo de Coco/administração & dosagem , Feminino , Idade Gestacional , Humanos , Recém-Nascido , Lauratos/administração & dosagem , Masculino , Monoglicerídeos/administração & dosagem , Sepse Neonatal/microbiologia , Sepse Neonatal/prevenção & controle , Ensaios Clínicos Controlados Aleatórios como Assunto , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/crescimento & desenvolvimento , Staphylococcus epidermidis/efeitos dos fármacos , Staphylococcus epidermidis/crescimento & desenvolvimentoRESUMO
Preterm infants are at risk of increased trans-epidermal water loss and infections due to epidermal immaturity. The emollient and anti-infective properties of coconut oil make it a potentially beneficial topical agent for this population. We aimed to systematically review randomised trials assessing the effects of topical coconut oil in preterm infants. Medline, EMBASE, Cochrane Central Register of Controlled Trials and CINAHL were searched. Seven trials (n = 727 infants) were included. The majority of trials included relatively mature infants (gestation > 32 weeks, birth weight > 1200 g). The duration of intervention (5-31 days) and outcomes of interest varied among included studies. Meta-analysis using random effects model found significantly lower incidence of hospital-acquired blood stream infections (HABSI) in the coconut oil group (11/164 vs 32/166; relative risk 0.35, 95% confidence interval 0.18, 0.67, p = 0.001; I2 = 0%, two RCTs). Overall, infants in the coconut oil group had decreased water loss, decreased infection rates, better growth and skin condition. There were no significant adverse effects associated with coconut oil application. The overall quality of evidence was considered moderate for the outcome of HABSI and low for the outcome of physical growth based on GRADE guidelines.Conclusion: Topical coconut oil application to the skin may be beneficial in preterm infants, but the quality of evidence is low to moderate. Adequately powered randomised controlled trials, especially in very preterm (< 32 weeks) and extremely preterm (< 28 weeks) infants, are needed. What is Known: ⢠Coconut oil has been used traditionally for topical application in terms of infants in Asian countries What is New: ⢠This systematic review found that topical application of coconut oil may reduce the risk of infection and improve weight gain and skin condition in preterm infants. However, the quality of evidence was considered to be moderate to low based on GRADE guidelines.
Assuntos
Anti-Infecciosos/uso terapêutico , Óleo de Coco/uso terapêutico , Desidratação/prevenção & controle , Emolientes/uso terapêutico , Doenças do Prematuro/prevenção & controle , Sepse Neonatal/prevenção & controle , Higiene da Pele/métodos , Administração Cutânea , Humanos , Recém-Nascido , Recém-Nascido Prematuro , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento , Aumento de PesoRESUMO
BACKGROUND: The immature fragile skin of preterm infants represents an inadequate protective barrier. The emollient and anti-infective properties of coconut oil make it a potentially beneficial topical agent for this population. OBJECTIVES: Our aim was to evaluate feasibility, safety, and the effects of topical coconut oil on skin condition in very preterm infants. METHODS: An open-label randomised controlled trial in preterm infants <30 weeks' gestation was conducted. Enrolled infants were randomised to receive either routine care or topical coconut oil (5 mL/kg) twice daily for 21 days, starting within 24 h of birth. The neonatal skin condition was the primary outcome, and was assessed using the Neonatal Skin Condition Score (NSCS) on days 1, 7, 14, and 21. The number of coconut oil applications was recorded to assess clinical feasibility and all enrolled infants were monitored for adverse effects of topical coconut application, such as skin irritation. RESULTS: A total of 72 infants born <30 weeks' gestation were enrolled (36 infants per arm), with comparable demographic characteristics. Topical application of coconut oil was feasible and without adverse effects. The NSCS was maintained in the coconut oil group throughout the intervention period, but deteriorated from a median (IQR) of 3 (3-4) on day 1 to 4 (4-4) on day 21 in the control group (p = 0.01). There were no differences in common neonatal outcomes, including sepsis, necrotising enterocolitis, retinopathy of prematurity, chronic lung disease, and mortality. CONCLUSIONS: Topical coconut oil maintained a better skin condition in very preterm infants without adverse effects. This simple, safe, and affordable intervention warrants further investigation.
Assuntos
Óleo de Coco/administração & dosagem , Infecção Hospitalar/prevenção & controle , Emolientes/administração & dosagem , Doenças do Prematuro/prevenção & controle , Administração Cutânea , Idade Gestacional , Humanos , Recém-Nascido , Recém-Nascido Prematuro , Pele/efeitos dos fármacos , Austrália OcidentalRESUMO
BACKGROUND: Reduced gestational age and low birthweight are associated with an increased risk of neonatal infections. However, the long-term risk of infection, especially in late preterm infants or those at near-normal birthweight, is unknown. We estimated whether rates of infection-related admissions to hospital for children in Western Australia were associated with age, gestational age, birthweight, and birth length. METHODS: We did a population-based, data-linkage study using total-linked, registry data from the Western Australia Birth Register of all liveborn, non-Indigenous Australian singleton births recorded from Jan 1, 1980, to Dec 31, 2010. We followed up individuals from birth-related hospital discharge to age 18 years, death, or end of 2010, and linked to data about subsequent admissions to hospital or death registrations. Gestational age was assessed from both the last menstrual period and from estimates based on ultrasonography. We categorised birthweight by 500 g bands and birth length by 5 cm bands, and approximated the reference ranges for both to the 50th percentile. Because size at birth and gestational age are strongly associated, we calculated Z scores for gestational-specific and sex-specific birthweight, birth length, and ponderal index. Our primary outcomes were the number and type of infection-related admissions to hospital. We used multilevel negative binomial regression to generate rate ratios (RR) for such admissions, identified by codes from the International Classification of Diseases, versions 9 and 10-AM. We adjusted the RRs for maternal age at delivery, birth year, birth season, parity, sex, 5-min Apgar score, delivery method, socioeconomic status, and bronchopulmonary dysplasia. FINDINGS: Of 719â311 liveborn singletons included in the analysis and followed up for 8â824â093 person-years, 365â867 infection-related admissions to hospital occurred for 213â683 (30%) children. Of the 719â311 children included in the analysis, 137â124 (19%) had one infection-related admission to hospital, 43â796 (6%) had two, 16â679 (2%) had three, and 16â084 (2%) had four or more. The 365â867 admissions to hospital included a diagnosis of infection of the upper respiratory tract for 174â653 (48%), the lower respiratory tract for 74â297 (20%), the gastrointestinal tract for 44â755 (12%), and a viral infection for 37â213 (10%). Infection-related rates of admissions to hospital increased by 12% for each week reduction in gestational age less than 39-40 weeks (RR 1·12, 95% CI 1·12-1·13), by 19% for each 500 g reduction in birthweight less than 3000-3500 g (1·19, 1·18-1·21), and by 41% for each 5 cm reduction in birth length less than 45-50 cm (1·41, 1·38-1·45). Gestational age-specific and sex-specific birthweight Z scores lower than the 25th to 50th percentile and birth length Z scores lower than the 10th to 25th percentile were associated with increased rates of infection-related admissions to hospital (eg, 1st-5th percentile RR 1·15, 95% CI 1·12-1·19, and 1·11, 1·07-1·14, respectively). Ponderal index Z scores lower than the 25th to 50th percentile were also associated with increased rates of infection-related admissions (eg, 1st-5th percentile RR 1·08, 95% CI 1·04-1·12). A gestational age of 41 weeks or later, a birthweight or birth length Z score above the 50th percentile, or a ponderal index Z score between the 75th and 95th percentile, were associated with modestly reduced rates of infection-related admissions to hospital. INTERPRETATION: Children who were born with reduced gestational age, birthweight, and birth length have persistently increased rates of infection-related admissions to hospital until age 18 years. Pregnancy outcomes should be optimised to prevent infection occurring in this population, especially in resource-limited settings where suboptimum intrauterine growth and moderate prematurity are common. FUNDING: Australian National Health and Medical Research Council.
Assuntos
Infecções Bacterianas/epidemiologia , Peso ao Nascer , Idade Gestacional , Armazenamento e Recuperação da Informação/estatística & dados numéricos , Admissão do Paciente/estatística & dados numéricos , Viroses/epidemiologia , Adolescente , Austrália/epidemiologia , Criança , Pré-Escolar , Feminino , Hospitalização/estatística & dados numéricos , Humanos , Lactente , Recém-Nascido , Vigilância da População , Gravidez , Resultado da Gravidez , Sistema de RegistrosRESUMO
There is a paucity of data on the effect of preterm birth on the immunological composition of breast milk throughout the different stages of lactation. We aimed to characterise the effects of preterm birth on the levels of immune factors in milk during the 1st month postpartum, to determine whether preterm milk is deficient in antimicrobial factors. Colostrum (days 2-5 postpartum), transitional milk (days 8-12) and mature milk (days 26-30) were collected from mothers of extremely preterm (<28 weeks of gestation, n 15), very preterm (28-<32 weeks of gestation, n 15), moderately preterm (32-<37 weeks of gestation, n 15) and term infants (37-41 weeks of gestation, n 15). Total protein, lactoferrin, secretory IgA, soluble CD14 receptor (sCD14), transforming growth factor-ß2 (TGF-ß2), α defensin 5 (HD5), ß defensins 1 (HBD1) and 2, IL-6, IL-10, IL-13, interferon-γ, TNF-α and lysozyme (LZ) were quantified in milk. We examined the effects of lactation stage, gestational age, volume of milk expressed, mode of delivery, parity and maternal infection on milk immune factor concentrations using repeated-measures regression analysis. The concentrations of all factors except LZ and HD5 decreased over the 1st month postpartum. Extremely preterm mothers had significantly higher concentrations of HBD1 and TGF-ß2 in colostrum than term mothers did. After controlling for other variables in regression analyses, preterm birth was associated with higher concentrations of HBD1, LZ and sCD14 in milk samples. In conclusion, preterm breast milk contains significantly higher concentrations of some immune proteins than term breast milk.
Assuntos
Fatores Imunológicos/análise , Leite Humano/imunologia , Período Pós-Parto/imunologia , Nascimento Prematuro/imunologia , Colostro/imunologia , Defensinas/análise , Feminino , Idade Gestacional , Humanos , Imunoglobulina A Secretora/análise , Interferon gama/análise , Interleucinas/análise , Lactação/fisiologia , Lactoferrina/análise , Receptores de Lipopolissacarídeos/análise , Muramidase/análise , Solubilidade , Nascimento a Termo , Fator de Crescimento Transformador beta2/análise , Fator de Necrose Tumoral alfa/análiseRESUMO
Group B streptococcus (GBS) is an important cause of early- and late-onset sepsis in the newborn. Preterm infants have markedly increased susceptibility and worse outcomes, but their immunological responses to GBS are poorly defined. We compared mononuclear cell and whole-blood cytokine responses to heat-killed GBS (HKGBS) of preterm infants (gestational age [GA], 26 to 33 weeks), term infants, and healthy adults. We investigated the kinetics and cell source of induced cytokines and quantified HKGBS phagocytosis. HKGBS-induced tumor necrosis factor (TNF) and interleukin 6 (IL-6) secretion was significantly impaired in preterm infants compared to that in term infants and adults. These cytokines were predominantly monocytic in origin, and production was intrinsically linked to HKGBS phagocytosis. Very preterm infants (GA, <30 weeks) had fewer cytokine-producing monocytes, but nonopsonic phagocytosis ability was comparable to that for term infants and adults. Exogenous complement supplementation increased phagocytosis in all groups, as well as the proportion of preterm monocytes producing IL-6, but for very preterm infants, responses were still deficient. Similar defective preterm monocyte responses were observed in fresh whole cord blood stimulated with live GBS. Lymphocyte-associated cytokines were significantly deficient for both preterm and term infants compared to levels for adults. These findings indicate that a subset of preterm monocytes do not respond to GBS, a defect compounded by generalized weaker lymphocyte responses in newborns. Together these deficient responses may increase the susceptibility of preterm infants to GBS infection.
Assuntos
Citocinas/imunologia , Recém-Nascido Prematuro/imunologia , Linfócitos/imunologia , Monócitos/imunologia , Streptococcus agalactiae/imunologia , Citocinas/biossíntese , Sangue Fetal/imunologia , Humanos , Recém-Nascido , Sepse/imunologia , Sepse/microbiologia , Infecções Estreptocócicas/imunologiaRESUMO
BACKGROUND: Staphylococcus epidermidis (SE) is a nosocomial pathogen that causes catheter-associated bacteremia in the immunocompromised, including those at the extremes of age, motivating study of host clearance mechanisms. SE-derived soluble components engage TLR2; but additional signaling pathways have also been implicated, and TLR2 can play complex, at times detrimental, roles in host defense against other Staphylococcal spp. The role of TLR2 in responses of primary blood leukocytes to live SE and in clearance of SE bacteremia, the most common clinical manifestation of SE infection, is unknown. METHODOLOGY/PRINCIPAL FINDINGS: We studied TLR2-mediated recognition of live clinical SE strain 1457 employing TLR2-transfected cells, neutralizing anti-TLR antibodies and TLR2-deficient mice. TLR2 mediated SE-induced cytokine production in human embryonic kidney cells, human whole blood and murine primary macrophages, in part via recognition of a soluble TLR2 agonist. After i.v. challenge with SE, early (1 h) cytokine/chemokine production and subsequent clearance of bacteremia (24-48 h) were markedly impaired in TLR2-deficient mice. CONCLUSIONS/SIGNIFICANCE: TLR2 mediates recognition of live SE and clearance of SE bacteremia in vivo.
Assuntos
Bacteriemia/imunologia , Staphylococcus epidermidis/imunologia , Receptor 2 Toll-Like/imunologia , Animais , Anticorpos , Sangue/microbiologia , Células Cultivadas , Citocinas/biossíntese , Imunidade Inata , Macrófagos/microbiologia , Camundongos , Camundongos Knockout , Transdução de Sinais/imunologia , Infecções Estafilocócicas/imunologia , Receptor 2 Toll-Like/deficiênciaRESUMO
BACKGROUND: Erythropoietin (Epo) was originally defined as a hematopoietic growth factor, but also has potent tissue-protective properties. The cytokine-modulating actions of Epo have received scant attention. We hypothesized that Epo significantly influences the in vitro cytokine production in both neonates and adults. METHODS: The effects of Epo were investigated using a standardized in vitro whole blood assay. Production of various cytokines was assessed by means of intracellular cytokine detection (IL-2, -6, -8, IFN-gamma and TNF-alpha) in preterm infants, term neonates and adults. Furthermore, synthesis of IL-4, -5 and -10 in adults was investigated via cytometric bead array. RESULTS: Epo significantly inhibits the production of various cytokines in preterm infants, term neonates and adults. In CD3+ lymphocytes, Epo predominantly decreases the number of IL-2-positive cells in all age groups. Similarly, in CD14+ cells, Epo significantly diminishes the number of IL-6- and TNF-alpha-producing cells. Furthermore, Epo significantly inhibits the synthesis of IL-4, IL-5 and IL-10 in adults. CONCLUSION: rhEpo has significant inhibitory potential on the production of various cytokines by leukocytes in preterm and term infants as well as in adults. The described effect likely contributes to the tissue protective properties of Epo.
Assuntos
Eritropoetina/farmacologia , Interleucinas/biossíntese , Leucócitos Mononucleares/efeitos dos fármacos , Fator de Necrose Tumoral alfa/biossíntese , Adulto , Técnicas de Cultura de Células , Humanos , Recém-Nascido , Recém-Nascido Prematuro , Interferon gama/biossíntese , Leucócitos Mononucleares/metabolismo , Proteínas RecombinantesRESUMO
PURPOSE OF REVIEW: To review current data on genetic factors contributing to the striking susceptibility of neonates to infectious diseases and other adverse outcomes. RECENT FINDINGS: Although few studies address genetic determinants of neonatal infectious disease susceptibility, several variants in genes involved in the innate immune response have been associated with differential risk for neonatal infection. The most consistent results relate to polymorphisms of tumour necrosis factor-alpha, whereas other gene polymorphisms, such as those of interleukin-6, have yielded conflicting findings. Similar genetic factors may be involved in other inflammatory neonatal diseases. Recent data suggest that genetic variation may influence the pace of immunologic maturation. SUMMARY: Despite the enormous human and financial costs of infection for neonatal mortality and morbidity worldwide, it remains unclear why neonates are so susceptible. Genetic epidemiologic studies may assist in the identification of critical protective and pathogenic pathways. Despite the current relative lack of robust data, such studies are likely to facilitate the development of interventions that ultimately decrease the significant morbidity and mortality of this highly vulnerable population.
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Doenças Transmissíveis/genética , Recém-Nascido , Doenças Transmissíveis/imunologia , Doenças Transmissíveis/microbiologia , Feminino , Predisposição Genética para Doença , Humanos , Interleucina-6/imunologia , Trabalho de Parto Prematuro/imunologia , Trabalho de Parto Prematuro/microbiologia , Gravidez , Fator de Necrose Tumoral alfa/imunologiaAssuntos
Doença de Lyme/diagnóstico , Mamilos , Dermatopatias/diagnóstico , Criança , Diagnóstico Diferencial , Feminino , Humanos , Doença de Lyme/patologia , Linfoma de Células B/diagnóstico , Linfoma de Células B/patologia , Dermatopatias/patologia , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/patologiaRESUMO
Newborns and especially preterm infants show a unique susceptibility to severe bacterial infections that cause significant morbidity and mortality. As very few data are available on innate immune functions in human fetuses, we conducted a comprehensive study to investigate the expression of several adhesion molecules essentially involved in migration (CD11a, CD11b, CD11c, CD18, and CD62L). Furthermore, phagocytic activity, generation of respiratory burst products, and production of several proinflammatory cytokines were assessed. Various functions of the fetal innate immune system were demonstrated to be essentially different from those observed in term neonates or adults. Expression of several surface markers was significantly diminished on fetal granulocytes. Furthermore, a significantly reduced phagocytic activity of fetal granulocytes and monocytes was found, contrasted by an enhanced generation of reactive oxygen products. In addition, we demonstrate that significant numbers of fetal monocytes are capable of the production of proinflammatory cytokines in response to stimulation. However, the pattern of cytokine production is different from the more mature individuals: the number of IL-6- and tumor necrosis factor-alpha-positive monocytes were significantly diminished, whereas more IL-8-producing monocytes were found compared with adults. The results of our study add significantly to our understanding of the maturation and impairment of the innate immune response.