Plasma Levels and Gene Expression of Granulocyte Colony-Stimulating Factor, Tumor Necrosis Factor-α, Interleukin (IL)-1β, IL-6, IL-8, and Soluble Intercellular Adhesion Molecule-1 in Neonatal Early Onset Sepsis

Abstract

Bacterial sepsis is still a leading cause of neonatal morbidity and mortality. Early onset sepsis in particular, presents with a different clinical course and involves other pathogens than sepsis later in life. In this study, plasma concentrations and mRNA expression of granulocyte colony-stimulating factor (G-CSF), tumor necrosis factor-alpha (TNF-alpha), IL-1beta, IL-6, IL-8, and soluble intercellular adhesion molecule-1 (sICAM-1) of neonates with early onset sepsis were evaluated in cord blood and during the first days of life. Irrespective of prematurity, plasma levels of G-CSF, TNF-alpha, IL-1beta, IL-6, and IL-8, but not sICAM-1, were excessively elevated in septic neonates when compared with both healthy infants and infants with clinically suspected but not confirmed sepsis. Compared with the corresponding maternal levels, neonatal cytokine cord plasma levels were likewise highly elevated, indicating the endogenous cytokine production by the neonate. With the exception of TNF-alpha, mRNA expression in blood cells from septic infants was, however, not more frequently detectable than in those from nonseptic patients. Cytokine levels decreased significantly within the first days of life, whereas levels of sICAM-1 and C-reactive protein increased during the same time period. In summary, in contrast to C-reactive protein and sICAM-1, cord blood plasma levels, but not the presence of mRNA, of G-CSF, TNF-alpha, IL-1beta, IL-6, and IL-8 can predict neonatal early onset sepsis with a high sensitivity and specificity. Cell types other than blood cells are likely to contribute considerably to the high cytokine production in septic newborns.

Reactive Hyperemia and Interleukin 6, Interleukin 8, and Tumor Necrosis Factor-α in the Diagnosis of Early-Onset Neonatal Sepsis

“…Because of frequent use of intrapartal antibiotics to the mother and only 1 blood culture obtained from the infant, we found few infants with positive blood/ spinal fluid cultures (17% in the sepsis group). A similarly small proportion of culture-proven infection also was found in other recent and larger studies of neonatal sepsis, 6,13 and this problem may limit the conclusions that can be drawn from the present data. However, the strict diagnostic criteria for clinical sepsis used in this study ensured that the infants assigned to this group were diagnosed correctly.…”

“…[3][4][5][6] Several studies have evaluated the role of cytokine determinations as early diagnostic markers in neonatal sepsis. [7][8][9][10][11][12][13] Although promising data have been published, problems with invasiveness, response time, and specificity remain to be solved. 7,8,14 -17 In sepsis, cytokines are involved in activating vascular and endothelial defense mechanisms that may cause changes in perfusion and vascular resistance in the microcirculation.…”

A readers' guide to the interpretation of diagnostic test properties: clinical example of sepsis

“…Because of the consequences of delayed diagnosis [2,3], physicians have low thresholds to initiate antibiotic therapy [4]. A plethora of tests has been suggested to improve diagnostic decision making in different clinical situations including sepsis, which is the example in this contribution [5,6,7].…”

Evaluation of IL-8-Concentrations in Plasma and Lysed EDTA-Blood in Healthy Neonates and Those with Suspected Early Onset Bacterial Infection

“…Neonates are susceptible to infections (1). The differential diagnosis of early-onset bacterial infection (EOBI) therefore must always be present for the neonatologist, regardless of how minor, unexpected, or discrete the clinical symptoms.…”

“…The differential diagnosis of early-onset bacterial infection (EOBI) therefore must always be present for the neonatologist, regardless of how minor, unexpected, or discrete the clinical symptoms. EOBI is usually defined as occurring up to 72 h after birth (2) and is associated with a high morbidity and mortality risk (1). The nonspecific clinical signs as well as the currently established biochemical and hematologic parameters have their diagnostic limitations (3,4) [reviewed in (5,6)].…”