EFFECTS OF INTERLEUKIN-8 ON THE DEVELOPING HUMAN INTESTINE

The human fetal/neonatal gastrointestinal tract is exposed to biologically significant concentrations of interleukin (IL)-8 swallowed with amniotic fluid and human milk. We hypothesized that IL-8 has a physiologic function in the developing human intestine. IL-8 was measured in preterm and term human milk, tested for stability under conditions simulating neonatal gastric and proximal small intestinal digestion, and its receptors were sought in human fetal bowel. The effect of IL-8 was then measured on intestinal cells in vitro. We observed that IL-8 is present in significant concentrations in human milk and that it is stable under conditions simulating digestion. Both IL-8 receptors, CXCR1 and CXCR2, are expressed extensively in the fetal intestine. When human fetal and adult intestinal cells are treated with rhIL-8 in vitro, there is a consistent increase in cell migration, proliferation, and differentiation. IL-8 also protects intestinal cells against chemical injury. These results suggest that besides its better-known role as a neutrophil chemoattractant, IL-8 has a trophic function in the developing human intestine.