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Identifier 000374445
Title Χημειοκίνες στις περιγεννητικές λοιμώξεις
Alternative Title Chemokines in perinatal infections.
Author Μανουρά, Αντωνία
Thesis advisor Γιαννακοπούλου, Χριστίνα
Reviewer Μπούμπας, Δημήτριο
Γεωργόπουλος, Γ.
Γκίκας, Α.
Ματαλλιωτάκης, Ι.
Σουγκλάκος, Ι
Abstract Neonatal sepsis is a life-threatening event affecting 3-5 neonates per 1000 live births. [1] Despite advances in neonatology, the threat of infection has not been eliminated, especially in preterm infants, leading to a substantial morbidity and mortality. [2,3] Neonatal susceptibility to infections is related to immature immunologic defense. [4] Recruitment of leucocytes to the site of pathogen invasion is an essential part of host’s response to infection. [5] Chemotactic cytokines, collectively known as chemokines, appear to have the capacity to control the movement of leukocytes and are crucial elements in this process [5,6] Chemokines are members of a family of homologous proteins with molecular weights in the range of 8-12 kD [5,6], subdivided into four families on the basis of the relative position of their cysteine residues. [5]. The α- (CXC) and β- (CC) chemokines, which contain four cysteines, appear to be the largest families. α-Chemokines predominantly recruit neutrophils and β-chemokines attract lymphocytes, monocytes, eosinophils, basophils and natural killer cells. [6] Chemotaxis is deficient in neonates, particularly those delivered prematurely, and this may contribute to their increased vulnerability to sepsis. [7] However the role of chemokines in neonatal infections, has not been extensively investigated, with the exception of IL-8. [8] Few studies have reported the neonatal chemokine response to infections. [9,10,11] Some chemokines (GRO-a, MCP-1, IP-10, and MIG) have been reported to be higher in infected than healthy neonates, while RANTES has been reported lower [9,10,11]. High levels of MIP-1α have been documented in adults. [12] Other chemokines, including ENA-78, have not been measured in infected neonates. Aim of the study The aim of this study was to investigate the magnitude of two a- (GRO-a, ENA-78) and two β- chemokines (RANTES, MIP-1a) serum concentration in term and preterm septic neonates. Materials and methods From January 2003 through December 2006, one hundred and twenty nine neonates admitted to the Neonatology Department at Heraklion University Hospital were included in the study. Seventy-one term and preterm neonates with signs and symptoms suggestive of systemic infection or necrotizing enterocolitis (NEC), requiring full sepsis evaluation and antibiotic treatment formed the study group. Fifty eight neonates, admitted at our Department for miscellaneous reasons other than infection were the control group. In order to evaluate differences in chemokines concentrations between term and preterm neonates, four subgroups were further formed: study group I (42 term infected neonates), study group II (29 infected preterm neonates), control group I (38 non-infected term neonates) and control group II (20 non-infected premature neonates). Neonates with evidence of major congenital malformations, inborn errors of metabolism or chromosomal anomalies were excluded from the study. Sepsis was defined when blood and/or cerebrospinal fluid cultures were positive along with supporting clinical findings. In case of negative blood culture, sepsis was defined when laboratory findings suggestive infection were present in combination with at least three symptoms or signs, compatible with infection. In the study group, two blood samples were obtained; the first, during sepsis evaluation, before initiation of antibiotic treatment and the second, after three to five days of initiation of treatment. In the control group, blood samples were obtained at the time of inclusion in the study. The blood samples were centrifugated and serum was separated and stored at -20oC until assay. Chemokine concentrations were determined by use of a commercially available immunoassay kit. Results Serum levels of Gro-a in the study group during infection were higher (433,8pg/ml vs 277pg/ml, p<0,001). Serum levels of RANTES in the study group were lower as compared to those of the control group (22445pg/ml vs 39490pg/ml, p<0,001). No significant difference was found in serum levels of MIP1-a and ENA-78. Furthermore, levels of Gro-a and RANTES were significantly different at day 0 as compared to levels at day 3-5. Levels of Gro-a were higher (433,8pg/ml vs 218,2 pg/ml) and levels of RANTES were lower (22445pg/ml vs 46325pg/ml) at day 0 as compared to those of day 3-5. Chemokine serum concentrations on day 3-5 in the study group did not differ significantly as compared to those of the control group. (433,8pg/ml έναντι 277pg/ml, p<0,001). Concentrations of GRO-1a and RANTES levels in subgroups of term and preterm stydy neonates were significantly different, as compared to their controls, while serum concentrations of ENA-78 and MIP-1a did not differ significantly between subgroups. RANTES serum levels of premature infants were significantly lower, both on day 0 and day 3-5, in the study group, as compared to those of term neonates. GRO-a, ENA-78 and MIP1-a did not differ significantly between the two groups. Conclusion Our findings suggest up-regulation of GRO-1a and down-regulation of RANTES at the onset of a septic episode, similar to the response pattern observed in septic adults. Both term and preterm neonates seem to have the potential to elicit a chemotactic response to infection.
Language Greek
Subject Chemokines
ENA-78
GRO-a
MIP-1a
Microbiology and immunology
Neonatal sepsis
Rantes
Νεογνική σηψαιμία
Χημειοκίνες
Issue date 2012-04-04
Collection   Faculty/Department--School of Medicine--Department of Medicine--Doctoral theses
  Type of Work--Doctoral theses
Permanent Link https://elocus.lib.uoc.gr//dlib/f/c/7/metadata-dlib-1337679261-396773-27438.tkl Bookmark and Share
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