G122(P) Melatonin and immune cell responses in neonatal encephalopathy. (27th April 2015) - Asalm, S
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.