Interleukin-8 and Monocyte Chemotactic Protein-1 mRNA Expression in Perinatally Infected and Asphyxiated Preterm Neonates

Abstract

Background: Inflammation due to perinatal infection (PI) and perinatal asphyxia (PA) may cause damage to various tissues and very often to the immature brain of the fetus and the newborn. Previously, we have shown that the neonatal immune system has the ability to produce increased chemokine protein levels in the serum during the inflammatory response caused by PI and PA. Aim: The aim of our present study was to investigate mRNA levels of the proinflammatory chemokines interleukin-8 (IL-8) and monocyte chemotactic protein-1 (MCP-1) in peripheral blood leukocytes from infected and asphyxiated neonates. Methods: Forty-two premature neonates were studied; 11 with PI, 16 with PA and 15 without PA and PI, were used as controls. IL-8 and MCP-1 mRNA levels were investigated in whole blood and in phytohemagglutinin-activated lymphocytes using semi-quantitative polymerase chain reaction and real-time polymerase chain reaction, respectively. Results: IL-8 mRNA levels were significantly increased in whole blood both during PA and PI, while MCP-1 mRNA levels were not. In vitro activated lymphocytes expressed significantly increased IL-8 mRNA levels during PI, whereas no increase was observed during PA. MCP-1 mRNA levels were significantly increased in activated lymphocytes during PA, while no increase was observed during PI. Conclusions: Our data show that chemokine mRNA levels expressed by activated lymphocytes during inflammation caused by PIs are different to those expressed during PAs. These findings might have important implications during the administration of specific chemokine antagonists in order to prevent or reduce tissue damage caused by inflammation.

Biomarkers for neonatal sepsis: recent developments

“…These multiple function secondary mediators cause activation of the coagulation cascade, the complement cascade, as well as participate in the production of prostaglandins, leukotrienes, proteases, and oxidants. As a result of these highly regulated factors, most adverse effects of sepsis such as SIRS, disseminated intravascular coagulation (DIC), septic shock, multiple organ dysfunction syndrome, and complement activated response syndrome are associated with an imbalance in the production of proinflammatory mediators [84][85][86][87] as well as the counterbalance synthesis of anti-inflammatory cytokines. Anti-inflammatory cytokines include IL-4, IL-10, tumor necrosis factor soluble receptor, IL-1 receptor alpha, and transforming growth factor beta 2 (TGF-β2).…”

“…As the circulating concentrations of inflammatory markers such as the cytokines, chemokines, and acute phase reactants may not fully represent the complete host response to an infection, these technologies push researchers to focus on chemokine mRNA expression and its relation to infection and other stressors such as birth asphyxia. 11,85 Recent reports demonstrate an association of elevated IL-8 mRNA expression in neonates exposed to perinatal infection compared to mRNA expression of IL-8 and MCP-1 expression changes in neonates with perinatal asphyxia. 85 Proteomic and metabolomics profiling technologies provide insight into the functional expression of proteins or metabolites present in a biological sample.…”

“…11,85 Recent reports demonstrate an association of elevated IL-8 mRNA expression in neonates exposed to perinatal infection compared to mRNA expression of IL-8 and MCP-1 expression changes in neonates with perinatal asphyxia. 85 Proteomic and metabolomics profiling technologies provide insight into the functional expression of proteins or metabolites present in a biological sample. The aim of proteomics is to obtain insight into the functional expression of proteins during neonatal sepsis, to identify different pattern of protein expression in different individuals with and without diseases, and to discover host response biomarkers that will be useful in the diagnostic process of an acute infection.…”

Biomarkers for Late-Onset Neonatal Sepsis: Cytokines and Beyond

“…One study measuring whole blood IL-8 and MCP-1 mRNA concentrations suggested that levels of both mRNAs were elevated in infants with perinatal asphyxia, whereas only IL-8 mRNA level was elevated in infants with perinatal infection. 47 The detection of tissue-specific mRNA could potentially be used as a basis for developing disease-specific biomarkers in neonates.…”

Hematologic profile of the fetus with systemic inflammatory response syndrome

“…FIRS is also associated with an increase in fetal plasma concentrations of soluble tumor necrosis factor receptors-1 and 2, IL-1β, IL-8 and C-reactive protein [3–10]. FIRS is associated with the impending onset of preterm labor/delivery, microbial invasion of the amniotic cavity and increased perinatal morbidity after adjustment for gestational age [11–24].…”