Early application of nerve growth factor affects serum inflammatory cytokine levels in neonatal hypoxic ischemic encephalopathy

Jingguo Chen; Huijuan Huang; Kaijun Zheng; Ronghua Xia; Jian Chen; Xiufang Yang; Chunhua Ye; Qiang Lin

摘要：BACKGROUND: It has been demonstrated that there are changes of various cytokines, chemokines and adhesion factors in neonatal hypoxic ischemic encephalopathy (HIE). What are the changes of interleukin-6 and interleukin-18 in serum of HIE neonates.OBJECTIVE: To observe the dynamic changes of interleukin-6 and interleukin-18 in peripheral serum at different time after HIE in neonates, and analyze the possible therapeutic efficacy of early application of NGF.DESIGN: A non-randomized controlled observation synchronically.SETTING: Department of Neonatology, Sun Yat-sen Hospital affiliated to Sun Yat-sen University.PARTICIPANTS: Sixty neonates with HIE were selected from the Department of Neonatology, Sun Yat-sen Hospital affiliated to Sun Yat-sen University from January 2004 to October 2006, including 32 boys and 28 girls, who were all accorded with the diagnostic standards for moderate to severe HIE. The neonates were divided into two groups NGF-treated group (n =30), HIE group (n =30). The HIE neonates in the NGF-treated group were given routine treatment and intramuscular injection of NGF within 24 hours after birth. Those in the HIE group were given routine treatments. Meanwhile, 30 apneic normal neonates (17 boys and 13 girls) at the same period were selected as the control group. The gestational age was 37 - 42 weeks in all the three groups, the body mass at birth was 2 500 - 4 000 g. Informed contents were obtained from the relatives of all the enrolled neonates.METHODS: The HIE neonates in the NGF-treated group were given routine treatment and intramuscular injection of NGF (2 000 U) within 24 hours after birth, once a day, 10 days as a course. Those in the HIE group were given routine treatments. Blood samples (3 mL) were drawn from femoral vein in all the neonates 1, 3 and 7 days after birth. The levels of interleukin-6 and interleukin-18 in serum were detected with enzyme-linked immunoabsorbent assay (ELISA).MAIN OUTCOME MEASURES: Serum levels of interlenkin-6 and interleukin-18 at 1, 3 and 7 days after birth.RESULTS: All the 60 HIE neonates and 30 normal neonates were involved in the final analysis of results.① Serum level of interleukin-6: The serum levels of interlenkin-6 at 1, 3 and 7 days after birth in the HIE group were all lower than those in the control group (P ＜ 0.05), and gradually recovered to the normal level as time prolonged. The serum levels of interleukin-6 at 1, 3 and 7 days after birth in the NGF-treated group were higher than those in the HIE group (P ＜ 0.05). ②Serum level of interleukin-18: The serum levels of interleukin-18 at 1, 3 and 7 days after birth in the HIE group were all higher than those in the control group (P ＜ 0.05), especially that at 3 days. The serum levels of interleukin-18 at 1, 3 and 7 days after birth in the NGF-treated group were lower than those in the HIE group (P ＜ 0.05).CONCLUSION: After hypoxic ischemia, the level of interleukin-6 was decreased and that of interleukin-18 was increased in peripheral serum in HIE neonates, while NGF could balance the levels of interleukin-6 and interleukin-18, adjust the immunological function, and protect the nerve cells.