Cytokines patterns in newborn infants with late onset sepsis

Abstract

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.

Detection of bacteraemia and host response in healthy neonatal foals

“…Inflammatory mediators of systemic inflammation, including cytokines interferon gamma (IFNγ), interleukin (IL) 1, IL‐6, IL‐18, IL‐2 and IL‐10, and chemokines IL‐8 and monocyte chemotactic protein 1 (MCP1), are upregulated in human neonatal sepsis . Though cytokines are known to be predictive of early sepsis in other neonatal species , there is limited knowledge of the foal host response to events and disease in early life.…”

New Biomarkers of Sepsis with Clinical Relevance

“…On the other hand, studies have reported that IL-6 shows great promise as a biomarker [60][61][62][63]. Like TNF and IL-1b, IL-6 is not altered only in sepsis; nevertheless, several studies have shown its importance in the prognosis of sepsis presenting strong correlations with patient mortality [62,63]. These results were also shown in an animal model of acute septic peritonitis (CLP) [61].…”

Effect of early-onset infections on expression of CD11a, CD11b, CD11c, CD18, CD54 and CD62L molecules on surface of neutrophils and monocytes from peripheral venous blood in preterm infants

“…In preterm infants, the reserve pool of granulocytes is smaller, and may be depleted faster than in full-term infants. The ability to accelerate the maturation of granulocytes is also reduced, which creates the risk of developing severe infections with poor prognosis [10,11,12,13]. It is believed, that in the early phase of inflammation, cytokine-induced leukocyte activation changes the expression of many adhesion molecules on the surface of granulocytes and monocytes.…”

“…U wcześniaków pula rezerwowa granulocytów jest mniejsza i może ulec szybszemu wyczerpaniu niż u noworodków donoszonych. Obniżona jest również zdolność przyspieszenia dojrzewania granulocytów w szpiku, co wiąże się z ryzykiem rozwoju zakażeń o ciężkim przebiegu i niepomyślnym rokowaniu [10,11,12,13]. Uważa się, że we wczesnej fazie zapalenia następuje aktywacja leukocytów indukowana cytokinami, co powoduje zmiany ekspresji wielu molekuł adhezyjnych na powierzchni granulocytów i monocytów.…”