Sepsis-Induced Immunosuppression in Neonates

Abstract

Neonates, especially those born preterm, are at increased risk of sepsis and adverse long-term effects associated with infection-related inflammation. Distinct neonatal immune responses and dysregulated inflammation are central to this unique susceptibility. The traditional separation of sepsis into an initial hyper-inflammatory response followed by hypo-inflammation is continually under review with new developments in this area of research. There is evidence to support the association of mortality in the early acute phase of sepsis with an overwhelming hyper-inflammatory immune response. Emerging evidence from adults suggests that hypo- and hyper-inflammation can occur during any phase of sepsis and that sepsis-immunosuppression is associated with increased mortality, morbidity, and risk to subsequent infection. In adults, sepsis-induced immunosuppression (SII) is characterised by alterations of innate and adaptive immune responses, including, but not limited to, a prominent bias toward anti-inflammatory cytokine secretion, diminished antigen presentation to T cells, and reduced activation and proliferation of T cells. It is unclear if sepsis-immunosuppression also plays a role in the adverse outcomes associated with neonatal sepsis. This review will focus on exploring if key characteristics associated with SII in adults are observed in neonates with sepsis.

Prenatal inflammation suppresses blood Th1 polarization and gene clusters related to cellular energy metabolism in preterm newborns

“…The increased immune suppression and reduced metabolic activities in LPS vs CON pigs are also similar to that observed in preterm vs term monocytes, 5 and in septic conditions. 8,42 This cellular programming pattern may reflect even a higher degree of disease tolerance strategy than that in preterm animals without prenatal insults, to avoid highly energy-consuming inflammatory responses following pathogenic encounters. In contrast, unlike the trends of decreased glycolysis and increased fatty acid oxidation in preterm vs term monocytes, our study showed that genes related to blood cellular glycolytic and fatty acid metabolic activities increased over time but did not differ between LPS and CON pigs after birth.…”

“…3 This host defense strategy may also explain the emerging evidence of neonatal sepsis to be associated with immunosuppression and increased circulating Treg frequencies. 6,8 A majority of the preterm births (up to 70%) are induced by prenatal insults, including chorioamnionitis (CA), inflammation of the fetal membranes. 9,10 It is, therefore, difficult to separate the effects of reduced fetal age at birth from prenatal inducing factors.…”

Commentary: Is the developmentally immature immune response in paediatric sepsis a recapitulation of immune tolerance?

“…critically analyzed sepsis and have associated immunoregulatory responses that are associated with immunosuppression with endotoxin tolerized states (17). However, we currently lack direct experimental evidence from clinical studies and relevant genomic analyses that can establish these distinctively altered immune responses during sepsis and associate these features with the age-related maturational states of the immune system (18,19).…”

Дифференцированный Подход К Диагностике Раннего Неонатального Сепсиса У Преждевременно Рожденных Детей

“…За даними статистики, в Україні захворюваність на неонатальний сепсис зростає, у 2018 році вона становила 0,69 на 1000 народжених живими [4]. Недоношеність і низька вага при народженні вірогідно пов'язані зі смертністю, що обумовлює медико-соціальну значимість даної патології в передчасно народжених дітей [5,6].…”