Inflammatory mediators in perinatal asphyxia and infection.

AIM: To determine serum levels of interleukin-6 (IL-6), IL-1beta, tumor necrosis factor-alpha (TNF-alpha), soluble intercellular adhesion molecule-1 (sICAM-1) and C-reactive protein (CRP) in asphyxiated neonates and compare these inflammatory factors with those found in neonates with perinatal infection. METHODS: 88 neonates were studied, of whom 36 were asphyxiated, 18 were infected and the remaining 34 were controls. Peripheral blood samples were obtained on the 1st, 3rd and 5th postnatal days. RESULTS: Cytokines IL-6 and IL-1beta as well as sICAM-1 serum levels did not differ between asphyxiated and infected neonates; however, at most time periods, their values were significantly higher than controls. TNF-alpha was similar in the three groups of neonates. CRP serum values were significantly higher in the infected neonates than in the asphyxiated or control subjects. Among the 54 asphyxiated and infected neonates, 15 were considered as severe cases and 39 as mild. The severe cases, at most time periods, had significantly higher IL-6, IL-1beta and sICAM-1 levels compared with the mild ones. Through receiver operating characteristic curves the cut-off points, sensitivities, and specificities for distinguishing neonates at risk or at high risk for brain damage were established. CONCLUSION: Similar increases in serum levels of IL-6, IL-1beta and sICAM-1 were found in perinatally asphyxiated and infected neonates. As these increases correlated with the severity of the perinatal insults, neonates at high risk for brain damage might be detected.

Interleukin-8 and monocyte chemotactic protein-1 mRNA expression in perinatally infected and asphyxiated preterm neonates.

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.

Early markers of brain damage in premature low-birth-weight neonates who suffered from perinatal asphyxia and/or infection.

We studied 57 low-birth-weight premature neonates, of whom 29 suffered from perinatal asphyxia and/or infection, while the remaining 28 did not and served as controls. We measured peripheral nucleated red blood cell (NRBC) absolute numbers as well as interleukin (IL)-1beta, IL-6 and tumour necrosis factor (TNF)-alpha cytokine serum levels at 24 h postnatally and on days 3 and 7 following birth. Fourteen of the asphyxiated/infected neonates and 12 controls had neurologic assessments at the corrected postnatal age of 18 months. We found NRBC absolute numbers and serum IL-1beta and IL-6 cytokine levels at 24 h postnatally to be significantly higher in neonates with perinatal asphyxia/infection than in the controls (p = 0.022, p = 0.036 and p = 0.037, respectively). TNF-alpha levels did not differ. Neurologic examination at the corrected postnatal age of 18 months showed 8 out of the 14 children who had been asphyxiated/infected as neonates to have abnormal findings, while 12 children who were used as controls during their neonatal period were normal. Abnormal neurologic findings correlated with high NRBC counts and IL-1beta and IL-6 levels at 24 h postnatally. In conclusion, increased NRBC counts and proinflammatory cytokine levels in asphyxiated/infected neonates represent early markers for subsequent neurologic impairment.