Immunity peculiarities of neonates in case of perinatal pathology

Materials and methods. The group of term infants with clinical signs of perinatal pathology (173 individuals) was examined. They were divided into two groups: group A included those with diagnosed severe forms of diseases (121 individuals), and group B included 52 infants with general moderate severity of perinatal pathology. The group of comparison included 82 newborns without substantial adaptive deviations after birth. IL1b and IL6 levels were examined by means of immunofluorescence method “Clonospectr” using the reagents produced by “ProCon”. Absolute and relative amount of СD2+-associated Т and NK-lymphocytes, СD14+-associated monocytes, СD15+-associated neutrophils, СD19+-associated В-lymphocytes and СD54+-associated ІСАМ-1 cells were determined by means of immunofluorescence method “Status” using the set of monoclonal and polyclonal antibodies produced by “Sorbent”. The data obtained were statistically processed with the application of applied programs package used for medical-biological studies Statgraphics Centurion XVI.I [2011] on the personal computer Pentium MMX CPU.


Introduction
Lymphocytes multiplication and differentiation are considered to be the functions of immune system that is associated with mediators of intercellular communication production and contact connection with adhesion molecules participation.Immune response mediators are able to penetrate through undamaged blood-brain barrier and change functional activity of "hypothalamus-pituitary-adrenal cortex" system due to direct influence on the processes of sanogenesis and pathogenesis in a child's organism in conditions of birth oxidative stress (OS) [2,[4][5][6].
Immune system as one of the regulating systems of the body stipulates short-term and long-term adaptation after birth formation.Imbalance of immune system components in conditions of birth stress and hypoxia causes system of organs functional disorders development and perinatal pathology formation.

Objective
To study peculiarities of immunological indices in case of neonates' perinatal pathology to detect their role in pathogenesis and formation of diseases severity.

Materials and methods
The group of term infants with clinical signs of perinatal pathology (173 individuals) was examined.They were divided into two groups: group A included infants with diagnosed severe forms of diseases (121 individuals), and group B included 52 infants with general moderate severity in conditions of perinatal pathology.The group of comparison included 82 newborns without substantial adaptive deviations after birth.
The data obtained were statistically processed with the application of applied programs package used for medical-biological studies "Statgraphics Centurion XVI.I" [2011] on the personal computer Pentium MMX CPU.

Results and discussion
The results of the conducted clinical-statistical investigation detected that severity of condition of newborns from group A at birth was caused by: severe asphyxia in 24 cases (19.0 %), moderate asphyxia with further deterioration of the condition -in 52 cases (41.3 %), hemolytic disease of newborns -in 22 cases (17.5 %), manifestation of intrauterine infection -in 14 cases (11.1 %), inborn pneumonia -in 2 cases (1.6 %), Pierre Robin syndromein 2 cases (1.6 %).Adaptive disorders among infants of group B during the first week of life were caused by: neonatal encephalopathy -in 42 cases (80.9 %), CNS traumatic damage -in 5 cases (9.5 %), hemolytic disease of newborns -in 4 cases (7.8 %) and manifestation of intrauterine infection -in 1 case (1.9 %).
An average assessment of group A newborns at the first minute of life was 5.0 ± 0.21 point, at the fifth minute -5.9 ± 0.23 with probable difference as compared to babies from the control group (7.1 ± 0.03 and 7.7 ± 0.09 point respectively), Р < 0.05.The assessment of newborns from group B at the first minute of life was 7.1 ± 0.08 point, at the fifth minute -7.8 ± 0.11 that was significantly higher than those of infants from group A, but did not differ from the control group.
The results of the studies were indicative of the fact that considerable differences in the level of proinflammatory cytokines IL1b and IL6 were manifested in newborns of the groups compared according to the severity of their condition which indicates a certain difference of cytokine reaction.Thus, in case of physiological course of early neonatal period in infants the level of IL1b was 16.9 ± 1.54 pcg/ml, IL6 level -1.1 ± 0.08 pcg/ml, with moderate pathology -27.9 ± 1.48 pcg/ml and 4.3 ± 0.25 pcg/ml respectively; with severe condition -21.2 ± 0.39 pcg/ml and 2.2 ± 0.10 pcg/ml respectively (P < 0.05).
One of the most important functions of the cytokine system is insurance of coordinated activity of immune, endocrine and nervous systems in a complex response of the body to stressful situation.Cytokine effect is implemented through their interrelation with specific cells membrane receptors [3,7].
It should be noted that according to scientific literature evidence [1,4], in spite of cytokine activation, moderate changes of their level in newborns are not associated with realization of hypoxia, inflammation, endotoxicosis or multiple-organ failure clinical signs.Support of systemic homeostasis in these cases is provided by a complex of mechanisms of reverse connection (proliferation and differentiation of lymphocytes) and increased level of antiinflammatory cytokines in the blood serum.
The indices of immune system cells receptor activity depending on the severity of newborns condition demonstrated that considerable deviations from the norm in infants was characteristic of a relative amount of CD2 + -associated Т-and NK-lymphocytes -the indices increased according to pathology severity increasing.Relative amount of CD14 + -associated monocytes in children was characterized by a tendency to increase in case of moderate condition and reduction of the index in case of its increase.Relative amount of CD15 + -associated neutrophils increased in newborns with moderate disorders of their general condition with probable increase of the index in case of severe pathology.Relative amount of CD19 +associated B-lymphocytes is characterized by certain reduction of the index in newborns with moderate pathology and significant increase in severe pathology.Moreover, considerable differences in a relative amount of CD54 + cells (ІСАМ-1) were observed in newborns according to their general condition degree of severity.If there were any clinical signs of moderate pathology a significant increase in CD54 + index was found, the severity of condition against the background of perinatal pathology was associated with its significant low level as to children from the group of comparison.
Correlation dependence between the presented indices of the immune system demonstrated the greatest number of correlation links in early neonatal period in infants with satisfactory condition.The adaptation processes intensity in moderate perinatal pathology was associated with changes of correlation coefficients and their vector.In case of severe pathology strong correlation disappeared, the new ones were formed with negative values provoked by immune imbalance, decreased regulatory capacity of the immune system and general adaptation processes of the organism.

Conclusions
1.An increasing level of IL1b and IL6 cytokines is determined in term neonates which characterizes the activation of anti-inflammatory mechanisms in the body in conditions of birth stress.
2. Severity of perinatal pathology in infants as compared to the control is associated with an increased level of IL1b and IL6 in case of moderate severity and decreased level of the indices in case of severe condition of a neonate which in this case is indicative of insufficient organism compensatory mechanisms in severe forms of perinatal pathology.
Prospects of further studies are connected with investigation of issues concerning metabolic correction to normalize mechanisms of organism adaptation in perinatal pathology.