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.

Eligibility Criteria:
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