Stimulation of neutrophil production in CSF-1-responsive clones

The hematopoietic growth factor CSF-1 has been considered relatively lineage specific for the production of macrophages, whereas GM-CSF elicits a predominance of neutrophils. It is likely that in vivo, individual clones are stimulated by the two CSFs, although the effect of dual stimulation on progenitors and their progeny has not been completely explored. We found that in cultures initiated with low concentrations of CSF-1 or GM-CSF, alone or in combination, production of macrophages predominated. Maximally stimulatory concentrations of CSF-1 elicited a predominance of macrophages, whereas maximal GM-CSF elicited many more neutrophil/macrophage colonies and pure neutrophil colonies. A combination of maximal CSF-1 and GM-CSF elicited the same differentiation as GM-CSF alone. Delayed addition of GM-CSF to cultures initiated with CSF-1 elicited colonies indistinguishable from GM-CSF alone, suggesting that neutrophil production had been switched on by GM- CSF. In mapping studies, colonies initiated by CSF-1 increased or switched on neutrophil production when GM-CSF was added as a second stimulus. These studies show that individual clones are responsive to both CSFs, and that the differentiating influence of GM-CSF predominates over that of CSF-1. In cultures to which only CSF-1 was added, a population of progenitors was sustained that produced neutrophils only after a GM-CSF stimulus. Thus, CSF-1 may participate in maintaining a reserve of progenitors for neutrophils during periods of increased neutrophil demand.     

Ghrelin Does Not Predict Adaptive Hyperphagia in Patients With Short Bowel Syndrome

Background: Adaptive hyperphagia is associated with reduced dependence on parenteral nutrition in patients with short bowel syndrome, but mechanisms have not been described. Ghrelin (GHR) has orexigenic effects, whereas peptide YY (PYY) reduces intake. GHR also acts as a hormone to control body fat stores. The authors evaluated whether GHR or PYY was related to caloric intake or absorption in patients with short bowel syndrome and whether GHR was associated with body mass index. Methods: Patients were admitted twice for nutrient balance. Height and body weight were obtained using standardized protocols. Energy intake >40 kcal/kg/day was defined as adaptive hyperphagia. Fasting plasma PYY and GHR were assayed in duplicate with Linco enzyme‐linked immunosorbent assay kits. Results: The median age of the 7 study participants was 62 (range, 45‐66) years, time with short bowel syndrome was 6.6 (range, 2‐29) years, and body mass index was 21.2 kg/m² (range, 19‐27.7). Five patients had adaptive hyperphagia. Neither GHR nor PYY was significantly related to energy intake or absorption (GHR: R = 0.22 and R = –0.233, PYY: R = 0.10 and R = –0.13). Body mass index trended toward an inverse association with GHR (GHR: R = –0.540, P = .211). Conclusion: The rigorous adaptive hyperphagia seen in these patients with short bowel syndrome was not related to fasting GHR or PYY, suggesting the need to explore other mechanisms.