Immunomodulation to Prevent or Treat Neonatal Sepsis: Past, Present, and Future

Abstract

Despite continued advances in neonatal medicine, sepsis remains a leading cause of death worldwide in neonatal intensive care units. The clinical presentation of sepsis in neonates varies markedly from that in older children and adults, and distinct acute inflammatory responses results in age-specific inflammatory and protective immune response to infection. This review first provides an overview of the neonatal immune system, then covers current mainstream, and experimental preventive and adjuvant therapies in neonatal sepsis. We also discuss how the distinct physiology of the perinatal period shapes early life immune responses and review strategies to reduce neonatal sepsis-related morbidity and mortality. A summary of studies that characterize immune ontogeny and neonatal sepsis is presented, followed by discussion of clinical trials assessing interventions such as breast milk, lactoferrin, probiotics, and pentoxifylline. Finally, we critically appraise future treatment options such as stem cell therapy, other antimicrobial protein and peptides, and targeting of pattern recognition receptors in an effort to prevent and/or treat sepsis in this highly vulnerable neonatal population.

The pattern of neonatal admissions and mortality at a regional and district hospital in the Upper West Region of Ghana; a cross sectional study

“…These measures can reduce the work load, shorten the duration of stay, avoid cross infection and reduce poor outcomes [30]. Newer interventions involving the use of immunomodulators such as lactoferrin, prebiotics, probiotics, synbiotics and pentoxifylline (ptx), a non-phosphodiesterase inhibitor can be introduced [31].…”

Cellular metabolism constrains innate immune responses in early human ontogeny

“…Despite decades of research into the functional characterization of the neonatal immune system, we lack an understanding of the mechanisms regulating PRR responsiveness during ontogeny 2 , 3 , 23 . To address this question, we studied responses to Candida spp ., a major neonatal pathogen that is recognized through multiple PRRs, and for which relatively little is known in human newborns.…”

Clinical and Biochemical Effects of Recombinant Human Granulocyte Colony-Stimulating Factor on the Prognosis of Preterm Infants with Early Onset Neonatal Sepsis

“…Small neutrophil pool is quickly depleted in infants if sepsis occurs, which leads to neutropenia, while Gram-negative sepsis is recovered somehow through the G-CSF use in preterm infants (47,48). Considering these data, the administration of G-CSF is suitable for management of infections in infants (49)(50)(51)(52). This can partially arise from a hyporesponsiveness of neonatal granulocytes to G-CSF associated with anti-apoptotic effects in comparison to adults (53).…”

“…However, it has been emphasized that G-CSF or GM-CSF can be effective for preterm infants with moderate (< 1700/µL) or severe (< 500/µL) neutropenia and systemic infection, respectively (50). In this regard, optimal timing of administration as well as monitoring of Gor GM-CSF levels are expected to maximize their positive contributions to these neonates (52).…”