BACKGROUND: Cytokines might be helpful to diagnose late onset sepsis (LOS) in newborn infants. Many studies on cytokines did not discriminate culture-proven from clinically-suspected sepsis; however, such differentiation is clinically useful. OBJECTIVES: To evaluate the feasibility to differentiate among culture-proven LOS, clinical LOS and controls using a battery of cytokines. STUDY DESIGN: This prospective study was conducted at the NICU of Harapan-Kita Women and Children's Hospital, Jakarta-Indonesia. Three groups of infants with postnatal age >72 hours of age were enrolled in the study: culture-proven sepsis group (PS) (n = 18), clinical sepsis group (CS) (n = 25) and control group (n = 34). A battery of 25 cytokines was measured in each infant five times: at enrollment, after 4 hrs, 12 hrs, 24 hrs, and 48 hrs using Invitrogen-immunoassays-Luminex TM 100. RESULTS: There were no significant differences in gestational age or mode of delivery among the three groups. IL-1, IL-2r, IL-6, IL-8, IL-10 and MIP-1a were significantly higher at all measurement points in group PS compared to controls. IL-13 was lower at all measurement moments in group CS compared to controls, IL-12 was lower and IP-10 higher between 0 and 24 hrs. IL-1Ra, IL-6, IL-8, IL-13, IL-15, TNF␣, MIP-1a and MIP-1b were higher at all the measurement moments in group PS compared to group CS. The ROC curves show that IL-6, IL-8, IL-15, MIP-1a, MIP-1b and TNF␣ have a sensitivity and specificity between 80 and 85% during the first 24-48 hours after the onset of infection. IL-6, IL-15, MIP-1a, MIP-1b and TNF␣ showed the best likelihood ratios. CONCLUSIONS: IL-6, IL8, IL 15, MIP-1a, MIP-1b and TNF␣ are potentially good markers for detecting a proven LOS. In case these cytokines are not elevated in sick infants, other causes than an infection have to be identified.
BackgroundNovel methods for cytokine analysis allow for the simultaneous measurement of 25 cytokines in 50 μL serum or plasma. Data on values of most of these cytokines in non-infected newborn infants are lacking. We analyzed levels of 25 cytokines in the first week of life in non-infected preterm and term infants and related them to gestational age.FindingsDuring the first week after birth, no trend over time was found in any of the cytokines, except for IL-1Ra and IL-6 where higher values were found in the first four hours. Between 24 and 72 hrs levels of IL-1Ra, IL-2, IL-8, IL-12, IL-13, IL-15, IL-17, IFNγ, MIP-1a, MCP-1, TNFα were lower in infants born after 30-32 wks compared to infants ≥36 wks; levels of IL-6, IL-10, IP-10 were lower in preterm infants of both 30–32 and 33–36 weeks. No difference between groups for any of the levels was found for IL-1b, IL-2r, IL-4, IL-5, IL-7, IFNa, MIP-1b, GM-CSF, Eotaxin and RANTES.ConclusionsLevels of 25 interleukines are stable in the first week of life in non-infected infants. Infants born after 30-32 wks showed lower levels of fourteen cytokines compared to infants born after more then 36 wks. This indicates a lower stimulation or activation of Th-1 cells, monocytes and dendritic cells in these infants.
These results challenge the hypothesis that calcineurin-induced reduction of Treg or TGF-beta expression predisposes nontransplanted tissue to inflammation, but indicate that combined immunosuppression hampers Treg development in the intestine.
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