DECREASED GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR PRODUCTION BY HUMAN NEONATAL BLOOD MONONUCLEAR-CELLS AND T-CELLS

Impaired production and delivery of neutrophils to the site of infection have been implicated in the increased susceptibility of the neonate to infection. Because granulocyte-macrophage colony-stimulating factor (GMCSF) and granulocyte colony-stimulating factor (G-CSF) play critical roles in the production of neutrophils from marrow precursors, we assessed the ability of leukocytes from neonates and adults to produce GM-CSF, G-CSF, and, for comparison, macrophage colony-stimulating factor (M-CSF) after stimulation with concanavalin A +/- phorbol myristate acetate [blood mononuclear cells (MC) and T lymphocytes] or lipopolysaccharide (monocytes). MC and monocytes from adult and neonatal subjects produced mRNA for GM-CSF, G-CSF, and M-CSF, whereas T cells produced only GM-CSF mRNA. Neonatal MC and T cells accumulated only approximately 30% as much GM-CSF mRNA as did adult MC and T cells. In contrast, the accumulation of GM-CSF mRNA by neonatal and adult monocytes was similar. Neonatal MC also accumulated similar amounts of G-CSF mRNA and somewhat more M-CSF mRNA than did adult MC; results with monocytes were similar to those with MC. Results of colony-stimulating activity bioassays on supernatants from neonatal and adult MC stimulated with concanavalin A paralleled the mRNA results. Although the overall number of colonies generated using neonatal and adult supernatants was similar, neonatal MC supernatants generated significantly more (p < 0.05) monocyte-containing colonies (72 +/- 19 versus 46 +/- 11), significantly fewer (p < 0.05) eosinophil-containing colonies (7 +/- 6 versus 23 +/- 13), and similar numbers of granulocyte-containing colonies (59 +/- 23 versus 63 +/- 11) compared with adult MC supernatants. Because GM-CSF is a major determinant of eosinophil production in these assays, these data suggested diminished amounts of GM-CSF in the neonatal culture supernatants. Similarly, GM-CSF concentrations in neonatal MC and T cell culture supernatants averaged 40 to 50% of the concentrations in adult culture supernatants as determined by ELISA (p < 0.01). Whether the modestly diminished GM-CSF production by neonatal T cells contributes to the observed deficiency of granulocyte production in neonates, which occurs when demand is increased in response to infection, remains to be determined.