Журнал «Здоровье ребенка» 3 (46) 2013

INTRODUCTION

One of the main functions of cytokines is to provide concerted action between immune, endocrine and nervous systems in the complex response of the body to a stressful situation. Physiological birth is a strong stress factor for the newborn, a situation is much worse in case of complications.

Participation of interleukin-1β (IL-1β) in stress reaction is determined by its influence on the level of glucocorticoids and central structures of the brain. The mentioned cytokine is one of the main triggers of the neuroendocrine stress response. It acts directly on neurosecretory cells of the hypothalamus and stimulates synthesis of the hypothalamic releasing factors, mainly - corticotropin-releasing hormone. This hormone causes activation of the hypothalamic-pituitary-adrenal axis. One of the consequences dysfunction of the hypothalamus-pituitary-adrenal system is increase secretion of cortisol.

The objective

To examine the neuro-endocrine stress response on the basis of study the dynamics of IL-1β and cortisol in serum during the neonatal period in newborns with kidney disturbance after asphyxia.

Materials and methods

100 full-term infants with a gestational age 38-41 weeks and signs of kidney damage were examined: 50 children who had severe asphyxia and 50 children with moderate asphyxia. The comparison group consisted of 20 children without birth asphyxia.

Renal dysfunction was diagnosed if creatinine level increased over 89 mcmol/l, blood urea more than 8 mmol/l, urine output less than 1 ml/kg per 1 hour. The diagnosis of moderate and severe asphyxia confirmed according to the "Protocol of resuscitation and post-reanimation newborn care" (Order of Ministry of Health of Ukraine dated 08.06.2007 №312). The serum interleukin-1β and cortisol levels were determined at 1-2, 7-8 and 25-30 days of life by ELISA.

Statistical data processing performed using the program Statistica 6.1 (StatSoft, USA). Our results were non-normally distributed, and therefore non-parametric testing was used such as Wilcoxon’s test. Correlations were calculated nonparametrically by Spearman's method. P values < 0.05 were considered significant.

Results

The content of IL-1β in comparison group placed within physiological borders (2,17-21,8 pg/ml). During the neonatal period level of IL-1β in healthy children was constant. It should be noted, that in 25%, 30% and 45% newborns of comparison group on 1-2, 7-8 and 20-30 days of life respectively cytokine levels were not determined.

In neonates who had renal dysfunction, regardless of the severity of asphyxia marked increase in IL-1β in serum at 1-2 days of life in 2,5 times (p <0,05).

On 7-8^th days of life in infants who had renal dysfunction after moderate asphyxia, the contents of IL-1β in serum reached maximum level. It was significantly higher than the same parameter on 1-2^nd days of life and exceeded (p <0,05) levels in the comparison group. Neonates with impaired renal function after severe asphyxia during this period had the highest level of IL-1β in serum. It is 1,5 times higher than the concentration in children with moderate asphyxia (p <0,05), 3.3 times higher than the content at 1-2 days of life (p <0,05) and almost 8 times higher than the rate in the comparison group (p <0,05).

Late neonatal period characterized a significant decrease IL-1β level in blood serum in both groups of examined children; but it content was 5-6 times yet higher than the rate in the comparison group. It should be noted that the difference between groups of children with asphyxia on the level of IL-1β was continued also at 25-30th days of life. Concentration of IL-1β was statistically higher in infants with impaired renal function due to severe asphyxia.

Interleukin-1β may affect the serum cortisol levels through the hypothalamus - pituitary - adrenal glands. Infants with kidney disturbance after moderate asphyxia were characterized by a significant increase serum cortisol concentration at 1-2^nd days of life (p<0,001). At the end of 1 week of life hormone content exceeded nearly 2 times the level in the comparison group. Reduced to physiological levels observed only at the end of neonatal period.

In children with renal damage after severe asphyxia noted the high value of serum cortisol levels in the first two days of life - 505,28 ± 36,96 nmol/l. To 7-8^th days content significantly decreased (p <0,05), but still higher than the rates in other groups of children. Late neonatal period observed inhibition of cortisol production. Its level in children with renal damage after severe asphyxia was the lowest among the examined groups of children.

Conclusion

1. Excessive production of interleukin-1β in neonates with renal disturbance after asphyxia causes neuro-endocrine stress response due to activation of the hypothalamic-pituitary-adrenal system and increase cortisol levels in blood serum.

2. Prolonged cytokine stimulation of the adrenal cortex in case of severe asphyxia causes depletion of cortisol production in late neonatal period.