Monocyte HLA-DR expression as predictor of poor outcome in neonates with late onset neonatal sepsis
Introduction
Monocytes play a critical role in immune regulation and host defense against foreign organisms. The important functions of these cells include phagocytosis, cytokine production, and presentation of antigen to lymphocytes for initiating both cellular and humoral immune responses. HLA-DR molecules which are important for presenting antigen to the CD4+ cells are expressed on the majority of monocytes and reflect the activation state of these cells.1, 2, 3
Down regulation of HLA-DR expression on monocytes has been reported in adult sepsis and different groups of surgical patients such as in cardiac surgery, transplantation, pancreatitis, and trauma and has been associated with septic complications and increased risk for fatal outcome.4, 5, 6, 7, 8, 9, 10
Neonatal sepsis can be categorized as early and late onset depending upon whether the onset of symptoms is before 72 h of life (early onset) or later (late onset). Late onset sepsis is caused by the organisms present in the external environment of the home or the hospital.11 Immaturity of the newborn immune system which encompasses all arms of the host response including cellular immunity, humoral immunity and innate immunity predispose the newborn infants to sepsis. All newborns initially have an immunological milieu skewed towards T helper cell type 2 immunity with diminished CD4+ T helper cell type 1 response when compared to adults. CD4+ T lymphocytes are essential for production of antibodies by B cells and for activation of CD8+ T lymphocytes. For activation of CD4+ T lymphocytes antigens have to be processed and presented by MHC-II molecules expressed by antigen presenting cells as mentioned above.12, 13
The aims of this study were, first to evaluate monocyte HLA-DR expression in late onset neonatal infection and second to investigate the prognostic value of monocyte HLA-DR expression at onset of symptoms for the final outcome.
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Patients and methods
We prospectively studied preterm and term newborn infants (postnatal age >3 days) who were followed up at the neonatal unit at Dr. Behcet Uz Children's Hospital, Izmir, Turkey between September 2007 and September 2008 for a suspected late onset neonatal infection. Consecutive patients were enrolled. Most of the patients were admitted from the outpatient setting. Minority of them especially the prematures were still in the hospital prior to inclusion in the study. Hematological and biochemical
Results
The clinical characteristics of the three study groups are summarized in Table 1. There were no significant differences among the groups regarding gestational age, birth weight, sex distribution and postnatal age (p > 0.05).
In the infection group 18 neonates (45%) were blood-culture positive, 5 for coagulase negative Staphylococcus, 4 for Candida spp., 2 for Escherichia coli, 2 for Klebsiella spp., 1 for Streptococcus spp., 1 for Staphylococcus aureus, 1 for Enterococcus spp., 1 for Sacharomyces
Discussion
The immune system plays a major role in the pathogenesis of sepsis and recent studies have shown that it is not a homogeneous entity. In the initial phase of sepsis there is systemic release of pro-inflammatory cytokines which are necessary for an effective inflammatory response against infection. Excess production of these has been associated with cellular injury, leading to death from multiple organ dysfunctions. Later, anti-inflammatory mediators are produced to modulate excessive
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