Dysregulation of expression of immunoregulatory and cytokine genes and its association with the immaturity in neonatal phagocytic and cellular immunity

Abstract

Background: Innate and adaptive immunity is comprised of cellular and humoral factors that provide rapid protection against microbial invasion. However, immaturity of innate and adaptive immune responses in the perinatal period predisposes the neonate to increased infectious morbidity and mortality from a variety of organisms.

Objectives: To elucidate dysregulation of expression of various immunoregulatory and cytokine genes and its association with the immaturity in neonatal phagocytic cellular immunity.

Methods: Comparison of protein production and mRNA of granulocyte macrophage colony-stimulating factor (GM-CSF), macrophage colony-stimulating factor (M-CSF), granulocyte colony-stimulating factor (G-CSF), interleukin (IL)-12, IL-15 and IL-18 in adult peripheral blood (APB) mononuclear cells (MNC) and cord blood (CB) MNC was studied. Effects of hematopoietic growth factors (HGFs, GM-CSF, M-CSF, G-CSF, IL-11) were studied in vivo in rats as well as randomized controlled studies conducted in neonates. Oligonucleotide microarrays were used to study gene expression patterns of activated CB and APB monocytes and dendritic cells.

Results and conclusions: We demonstrated dysregulation of various immunoregulatory and cytokine genes in CB MNC. This dysregulation may in part explain the immaturity of neonatal cell-mediated immunity. There are probably various dysregulated cytokines yet to be discovered. Biological agents such as IL-2, IL-12, IL-11 and/or IL-18 alone or in combination with HGFs should be considered for future studies to identify new approaches to enhance neonatal host defense, and thereby decrease the incidence of neonatal sepsis and the consequent high risk of morbidity and mortality.