Cytokine soluble receptors in perinatal and early neonatal life.

BACKGROUND: In contrast to cellular receptors, soluble receptors do not enhance the cellular activation because they do not have transmembranic and cytoplasmic parts, acting thereby as endogenous regulatory mechanisms against systemic functions of cytokines. AIM: To measure serum concentrations of the soluble interleukin-2 receptor (sIL2R), soluble interleukin-4 receptor (sIL4R), soluble interleukin-6 receptor (sIL6R), and soluble tumor necrosis factor-alpha receptor I and soluble tumor necrosis factor-alpha receptor II, during the perinatal and early neonatal period, in order to evaluate their role in activation of immune response in labor and the first days postpartum. METHODS: Soluble receptor serum concentrations were determined by enzyme-linked immunosorbent assay, in 45 healthy, full-termed neonates during the first and fifth days after birth, in 25 of their mothers (MS), in 25 samples of umbilical cords (UC) and in 25 healthy adult donors age-matched with the mothers (controls). RESULTS: Soluble receptor serum concentrations showed considerable changes during labor and early neonatal life, being significantly higher both in MS (except sIL6R) and in neonatal sample UC, first and fifth days after birth, compared with controls (p<0.0001). Neonatal serum sIL2R and sIL6R increased significantly from birth to the fifth day, while the remaining receptors showed a rapid increase in the first day (p<0.0001), declining significantly thereafter (p<0.0001). CONCLUSION: Our findings suggest that the elevated concentrations of all studied soluble cytokine receptors reflect the activation of immune response, and represent also regulatory protective mechanisms for mother and fetus-neonate against the systemic function of cytokines during labor and early neonatal life

Age-related differentiations of Th1/Th2 cytokines in newborn infants.

OBJECTIVE: To evaluate age-related differentiation of immune response in newborns by measuring serum concentrations of interleukin-2 (IL-2), interleukin-4 (IL-4) and interferon-gamma (IFN-gamma) during the perinatal period. SUBJECTS AND METHODS: Fifty-seven healthy term neonates, their mothers and 25 healthy adults (controls) age-matched to the mothers were included in the study. Cytokine concentrations were measured in the umbilical cord (UC), and in first-day (1N) and fifth-day (5N) neonatal samples, compared with those in maternal serum (MS) and control serum samples. RESULTS: Serum IL-2 concentrations in the UC were markedly elevated compared with those in MS and controls (p < 0.0001), decreasing significantly thereafter up to 5N (p < 0.001). IL-4 serum concentrations did not differ significantly between the UC, 1N and 5N samples; they were, however, markedly elevated compared with those in MS (p < 0.001, p < 0.0007 and p < 0.0001, respectively) and controls (p < 0.05, p < 0.01 and p < 0.006, respectively). IFN-gamma serum concentrations were significantly lower in the UC compared with those in controls (p < 0.04), increasing significantly up to 5N (p < 0.03). Both IFN-gamma/IL-2 and IFN-gamma/IL-4 ratios increased significantly in 5N, compared with those in the UC (p < 0.001 and p < 0.03). CONCLUSION: Our findings indicate a differential cytokine balance at birth with enhanced expression of IL-2 and IL-4 against IFN-gamma. However, a regularization of immune response seems to proceed quickly during the early neonatal life

Cytokines in neonatal serum

This thesis refers to the presence of selected cytokines (IL-2, IL-4, IFN-γ, IL-1β, IL-6 and TNF-α) and their receptors (sΙL-2R, SIL-4R, sΙL-6R, sTNFRI and sTNFRII) which are related with type 1 (Th1) and type 2 (Th2) of immune response and inflammation in the serum of pregnant women (MS) in the 1s t stage of labor, in the umbilical cord (UC) and in neonates at the 1st (1N) and the 5th (5N) day after birth, in order to evaluate their role in the development of the immune system in the early neonatal period. Serum samples were obtained from 97 healthy neonates and 52 pregnant women who gave birth in Aretaieion Hospital of Athens. Both cytokines and their receptors were determined by immunoenzyme techniques (microelisa), using commercially available Kits. All determined cytokines and their receptors a) showed significant alterations during the perinatal period and the first days after birth, b) were found significantly elevated during the 1st day of life, c) were significantly higher in the neonatal samples UC, 1N, and 5N, d) most of the determined cytokines in maternal and neonatal samples showed a strong dependence on the mode of delivery, being higher in the cases of vaginal delivery compared with those of elective caesarian section. In conclusion, the relative immunodeficiency of the neonates is most likely an adaptive mechanism to optimize survival by balancing the conflicting immunologic requirements of life in utero with those of external environment.Η διδακτορική αυτή διατριβή αναφέρεται στη διερεύνηση της παρουσίας επιλεγμένων κυτταροκινών (IL-2, IL-4, IFN-γ, IL-1β, IL-6 και TNF-α) και των υποδοχέων τους (sIL-2R, SIL-4R, SIL-6R, sTNFRI και sTNFRII) που συνδέονται με την τύπου 1 (Th1) και 2 (Th2) ανοσιακή απάντηση και τη φλεγμονή, στον ορό της μητέρας (ΟΜ) κατά την έναρξη του τοκετού, στον ομφάλιο λώρο (ΟΛ), και στα νεογνά, την 1η (1Ν) και 5η ημέρα (5Ν) μετά τον τοκετό, με σκοπό την αξιολόγηση του ρόλου τους στην ανάπτυξη του ανοσοποιητικού συστήματος κατά την πρώιμη νεογνική περίοδο. Το υλικό περιλαμβάνει 97 υγιή νεογνά και 52 επίτοκες σε τελειόμηνο φυσιολογική μονόδυμη κύηση, από περιστατικά της Β' Μαιευτικής και Γυναικολογικής Κλινικής Π.Α. στο Αρεταίειο Νοσοκομείο. Οι προσδιορισμοί των κυτταροκινών και των υποδοχέων τους διεξήχθησαν με πολύ ευαίσθητες ανοσοενζυμικές τεχνικές (microelisa). Οι τιμές των κυτταροκινών και των υποδοχέων τους α) παρουσιάζουν σημαντικές μεταβολές κατά την περιγεννητική και την πρώιμη νεογνική περίοδο, β) είναι στατιστικώς σημαντικά υψηλότερες στα δείγματα ΟΛ, 1Ν και 5Ν, σε σχέση με τους ενήλικες, γ) εμφανίζουν απότομη άνοδο στα δείγματα 1 Ν, δ) στον ορό της μητέρας ή/και στα νεογνικά δείγματα εξαρτώνται σημαντικά από το είδος του τοκετού, με υψηλότερες στις περιπτώσεις φυσιολογικού κολπικού τοκετού, σε σχέση με την προγραμματισμένη καισαρική τομή. Παρατηρείται διαταραχή της σχέσης IFN-γ/IL-2 και ΙFN-γ/ΙL-4 στον ΟΛ, εις βάρος της IFN-γ η οποία βελτιώνεται την 5η ημέρα ζωής. Συμπερασματικά, η σχετική ανοσοανεπάρκεια είναι πιθανόν ένας μηχανισμός προσαρμογής, προκειμένου το νεογνό να βελτιστοποιήσει την επιβίωση του, ισορροπώντας τις αντιφατικές ανοσολογικές απαιτήσεις της ενδομήτριας ζωής με αυτές του εξωμήτριου περιβάλλοντος

Post-cataract surgery endophthalmitis outbreak caused by multidrug-resistant Pseudomonas aeruginosa

In June 2010, a severe outbreak of 13 cases of post-cataract surgery endophthalmitis caused by multidrug-resistant Pseudomonas aeruginosa occurred. Pulse-field gel electrophoresis in eye isolates found 95% genetic similarity; however, extensive environmental and carriage investigation revealed no source of infection. Copyright (C) 2012 by the Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved

Clonal spread of KPC-2 carbapenemase-producing Klebsiella pneumoniae strains in Greece

KPC-possessing Klebsiella pneumoniae have been found to be widespread in several regions but are still rarely detected in Europe. We describe the characteristics of an outbreak caused by KPC producers in a tertiary care Greek hospital. During a 12 month period (October 2007-September 2008), 47 patients in Hippokration University Hospital yielded K. pneumoniae isolates that exhibited reduced susceptibility to carbapenems and were phenotypically positive for carbapenemase production but negative for metallo-beta-lactamase (MBL) production. Single patient isolates were tested by Vitek 2, Etest, agar dilution MICs, phenotypic assays and PFGE. Carbapenemase and other beta-lactamase genes were identified by PCR and sequencing. Patient records were retrospectively reviewed to access co-morbidities, antibiotic exposure prior to infection and outcome. The 47 K. pneumoniae isolates exhibited various susceptibilities to imipenem and meropenem; all were non-susceptible to ertapenem and several other antibiotics but most were susceptible to gentamicin, colistin and tigecycline. PFGE classified the isolates into two clonal types, with the predominant type, which was closely related to that of hyperepidemic strains from the USA and Israel, comprising three subtypes. All isolates carried the bla(KPC-2) gene; 45 also carried bla(SHV-12) and 29 bla(TEM-1). Patients were hospitalized in nine different units. The median length of hospital stay prior to KPC isolation was 21 days; 38 patients (80.9%) had evidence of clinical infection due to a KPC producer and 16 (34%) had bacteraemia. The crude mortality rate was 27.7%. A beta-lactam/beta-lactamase inhibitor combination was the most frequently administered antimicrobial prior to KPC isolation (20 patients; 42.5%), whereas only nine patients (19.1%) had prior carbapenem use. This study presents for the first time a wide intrahospital spread of KPC-producing K. pneumoniae clones in a European hospital. The KPC producers were rapidly disseminated in several units, indicating the difficulty in restraining such multidrug-resistant clones when they have been established in a hospital environment