Decreased Stimulated GM-CSF Production and GM-CSF Gene Expression but Normal Numbers of GM-CSF Receptors in Human Term Newborns Compared with Adults

Abstract

ABSTRACT. We investigated cord and adult production of granulocyte-macrophage colony-stimulating factor (GM-CSF), expression of GM-CSF mRNA from unstimulated and activated mononuclear cells, and the affinity and presence of GM-CSF receptors on mature effector cells in an attempt to better understand the underlying pathophysiology of altered neonatal host defense. Utilizing '251-GM-CSF as a ligand, Scatchard analysis revealed the presence of a single class affinity GM-CSF receptor with similar binding characteristics on both cord and adult peripheral P M N (kd = 44 and 39 pM) for adult and cord,

Decreased G-CSF and IL-3 Production and Gene Expression from Mononuclear Cells of Newborn Infants

“…Additionally, our study did not determine whether the decrease in G-CSF or IL-3 production from cord MNC was secondary to a decrease per MNC or a decrease in the specific subpopulation of G-CSF and IL-3 producing MNC. These results are consistent with our previous findings demonstrating negligible amounts of cord serum GM-CSF and decreased GM-CSF production after stimulation of cord MNC (32).…”

Granulocyte and Granulocyte-Macrophage Colony-Stimulating Factors in Cord and Maternal Serum at Delivery

“…Our findings are in keeping with those of Cairo et al (37,38), who were unable to demonstrate G-CSF or GM-CSF in cord sera of full-term neonates using an ELISA, but our results are at variance with those of Laver et al (36), who found high levels of both G-CSF and GM-CSF in full-term cord sera using a bioassay. This discrepancy may be accounted for by the different assay techniques used.…”

Cytokines Enhance Opsonophagocytosis of Type III Group B Streptococcus

“…20,21,30,39,40 The basal concentrations of GM-CSF in neonatal sera are negligible, and decreased GM-CSF expression and production may contribute to the development of neutropenia. 13,14 In a recent clinical trial, administration of recombinant human GM-CSF to premature infants was well-tolerated, and peripheral blood PMN counts and CR3 receptor expression were significantly increased. 30 Although GM-CSF may increase N-PMN count and function, type III GBS is most efficiently killed by PMNs when opsonized with complement and capsular polysaccharide-specific Ab.…”

“…Furthermore, the previously demonstrated priming for oxidative metabolism that occurs with GM-CSF treatment may have contributed to the enhanced microbial killing observed. 19 Although the production of GM-CSF by neonatal mononuclear cells may be reduced, [12][13][14] it also has been shown that the bactericidal activity of N-PMNs can be increased by GM-CSF. 19 Deficiencies in neonatal host defenses contribute to susceptibility to GBS infections.…”

“…[7][8][9][10][11] Several investigators have proposed that a deficiency in the production of or response to these cytokines may contribute to increased susceptibility to infection in neonates. 4,[12][13][14] TNF-␣ is an important mediator in the response of the host to infection and stimulates PMNs by inducing alterations in cell migration, adhesion, oxygen radical production, and degranulation. 15 TNF-␣ as a major monocyte product also increases complement receptor 1 (CR1) and CR3 expression on mature blood PMNs, thereby increasing margination and phagocytic activity.…”