G122(P) Melatonin and immune cell responses in neonatal encephalopathy

Abstract

Introduction Infection and inflammation can be antecedents of Neonatal Encephalopathy (NE) and increase the risk of neurological sequelae. Melatonin is a potent immunomodulator and antioxidant (1) and may alter the systemic inflammatory response in NE (2). Aim To investigate the in vitro effect of melatoninon whole blood reactive oxygen intermediates (ROI), CD11b and Toll-like receptor (TLR)-4 in neutrophils and monocytes from infants with NE receiving therapeutic hypothermia (TH) versus healthy neonatal controls in the first week of life. Methods Infants with NE were recruited and their demographics details, grade of NE, MRI results, outcome and placental histology were recorded. Whole blood was taken on Day 1,3 and 7 of life (NE group) and day 1(Controls) and flow cytometry used to assess TLR4, CD11b and ROI in both monocytes and neutrophils in the presence of Lipopolysaccharide (LPS) and/or melatonin. Ethics was received from ethics committee at National Maternity Hospital. Results LPS–induced ROI production was significantly increased in both neutrophils and monocytes (p = 0.03) in NE versus controls (n = 6) on day 1 of life. On day 7 of life, following TH, LPS-induced CD11b upregulation was significantly decreased by melatonin in vitro in neonates with NE (n = 7). There was no difference in TLR4 expression in NE and controls. Conclusion Melatonin decreases the production of CD11b in neutrophils, which is a marker of neutrophil activation and migration and may ameliorate the augmented systemic inflammatory response seen in infants with NE.