Modulation of human neutrophil apoptosis by gut hormones

Background: Inhibition of neutrophil apoptosis seems to be a prominent feature in inflammation, parenchymal damage, and unresolved organ dysfunction. Agents that modulate neutrophil apoptosis could alter the course of the disease. A variety of endogenous peptides, including some GIT hormones, have been reported as modulators of apoptosis in several types of cells. Objectives: We aim to study the effect of the GIT hormones VIP, gastrin, secretin, GIP and CCK on the in vitro viability of human neutrophils and the associated caspase changes. Methods: Neutrophils were prepared from the venous blood of twenty healthy male volunteers using density gradient centrifugation. Neutrophils were cultured in RPMI and treated with two concentrations of each of the five hormones and incubated for 1, 2, 4 and 6 hours. Viability was assessed by a kit that measured ATP levels. Caspase 3/7, caspase 8 and caspase 9 were measured using specific kits. Results: VIP accelerated apoptosis causing a 15 – 32% decrease in neutrophil viability in 11 of the twenty volunteers. VIP increased the levels of caspase 8 and caspase 3/7. Gastrin suppressed apoptosis causing a 17-30% increase in neutrophil viability in 7 of the twenty volunteers. However, VIP inhibited apoptosis in one subject and gastrin accelerated apoptosis in two subjects. The effects of secretin, GIP and CCK were not marked. Conclusions: The modulatory effects of VIP and gastrin on human neutrophil apoptosis are seen in a proportion, not all, of the population. VIP is more consistent in its effects than gastrin.