Granulocyte colony-stimulating factor is present in human milk and its receptor is present in human fetal intestine

Objective. Human milk provides neonates with a meaningful degree of protect ion from infection, but the responsible mechanisms are not well understood. Discovering these mechanisms is important, because of the possibility of s upplementing infant formulas with factors that simulate human milk's protec tive capacity. We postulated that granulocyte colony-stimulating factor (G- CSF), a cytokine known to augment antibacterial defenses through its saluto ry effect on neutrophil production, might be one such factor. To test this hypothesis, we quantified G-CSF in milk of healthy women and those with int raamniotic infection, and sought the presence of functional G-CSF receptors (G-CSF-R) in fetal/neonatal intestinal villi. Study Design. G-CSF was measured by enzyme-linked immunoassay in 126 milk s amples obtained from breast-feeding women, and the concentrations were anal yzed according to gestational age, postpartum day of collection (first 2 da ys vs greater 2 days), and the presence versus absence of intraamniotic inf ection. G-CSF-R messenger ribonucleic acid transcripts were sought from fet al/neonatal intestine using reverse transcriptase polymerase chain reaction , and localized using in situ RT-PCR. G-CSF-R protein, and specific intrace llular signaling proteins (Janus tyrosine kinase-1, Janus tyrosine kinase-2 , and tyrosine kinase-2), were sought by immunohistochemistry. Results. All milk samples contained G-CSF, and significantly more G-CSF was contained in milk collected during the first 2 postpartum days than during subsequent days. Milk from women who delivered prematurely had less G-CSF during the first 2 postpartum days than milk from women who delivered at te rm. When intraamniotic infection was present, the concentration of G-CSF in milk was elevated significantly compared with concentrations in milk of no ninfected women. G-CSF concentrations were also higher in milk collected du ring the first 2 postpartum days from women who had received intrapartum re combinant G-CSF treatment, compared with milk obtained from women with intr aamniotic infection, regardless if they delivered prematurely or at term. G -CSF-R messenger ribonucleic acid and protein were expressed on fetal villu s enterocytes, and Janus tyrosine kinase-1, Janus tyrosine kinase-2, and ty rosine kinase-2 were present within the cytoplasm of these cells. Conclusions. Human milk contains substantial quantities of G-CSF. G-CSF-R a re abundant on villus enterocytes, and specific proteins associated with G- CSF-R signaling are present in these cells.