The Role of Neutrophil CD64 and Soluble Triggering Receptor Expressed on Myeloid Cells 1 in Neonatal Sepsis
The Role of Neutrophil CD64 and Soluble Triggering Receptor Expressed on Myeloid Cells 1 in Neonatal Sepsis
Neonatal sepsis (NS) is a rather serious but relatively common health problem. Despite recent
 advances in the treatment of neonatal infection, mortality and comorbidities remain high.
Neonatal sepsis is a major contributor to an estimated 2.6 million annual deaths and accounts
 for approximately 3 % of all disability-adjusted life years. The consequences of NS can be
 minimized by early initiation of antibiotic therapy. Due to high NS rates, the vulnerability
 of the organism in the neonatal period and concerns about consequences (considerable
 mortality, association with other acute or chronic complications), antibiotic therapy is
 com¬monly started in clinical practice even though non-spe¬cific clinical signs develop. This
 is in spite of the fact that antibiotic overuse is linked to major negative outcomes. The
 reliable and early diagnosis of NS is therefore essential but, unfortunately, rather
 difficult.

 Probably the most widely used "biochemical" marker of NS, C-reactive protein (CRP), is one of
 the so-called late markers. Its sensitivity is mainly low in the early stages of infection;
 its reliability increases, particularly with serial measurements. In that case, its
 negativity practically rules out the presence of NS. It is not completely specific for NS.
 Procalcitonin (PCT), an intermediate marker, is relatively specific, providing prognostic
 information as well; it decreases rapidly in response to effective therapy. However, its
 complex postnatal "physiological" dynamics makes its measurements difficult, particularly in
 early-onset sepsis.

 CD64 is normally expressed in very low concentrations by unstimulated neutrophils. It is
 considerably upregulated on the trigger of bacterial invasion and has been shown to be
 involved in the process of phagocytosis and intracellular killing of pathogens. More
 importantly, neutrophils from preterm infants express CD64 during bacterial infections to the
 same degree as those from term infants, children, and adults. So in newborns, neutrophil CD64
 have been found to be promising markers for diagnosis of early and late infections.

 Among several candidate receptors, triggering Receptor Expressed on Myeloid cells 1 (TREM-1)
 appears to play a relevant role in the modulation of innate immunity, amplifying or
 attenuating Toll-Like Receptor (TLR)-induced signals. TREM-1 is a receptor of the
 immunoglobulin superfamily, expressed on human neutrophils and monocytes. In the early phase
 of infection, the engagements of Pattern Recognition Receptors (PRRs) by microbial components
 induce up-regulation of TREM-1. After recognition of a still unknown ligand, TREM-1
 associates with a signal transduction molecule called DAP12, triggering the sustained release
 of pro-inflammatory cytokines (TNF-alpha and IL-1b) and chemokines (IL-8 and monocyte
 chemotactic protein), which may result in prolonged survival of neutrophils and monocytes at
 the inflammatory site.
Inclusion Criteria:

 -  Sepsis was defined as a positive blood culture in infants with clinical and laboratory
 findings of infection. Manifestations of sepsis include poor suckling, sleepiness,
 respiratory distress, apnea, poor perfusion, cyanosis, bradycardia, fever or
 hypothermia, feeding intolerance, and neurological signs (as seizures). Routine sepsis
 evaluations included complete blood count, C-reactive protein, and blood culture.

 Exclusion Criteria:

 -  malformations

 -  prematurity

 -  Apgar score less than seven

 -  on antibiotics treatment before the start of the study