Immunomodulation of peritoneal macrophages by granulocyte-macrophage colony-stimulating factor in humans

Colony-stimulating factors are growth factors which induce differentiation of the hematopoietic stem cells. Granulocyte-macrophage colony-stimulating factor (GM-CSF) stimulates proliferation and improves functions of neutrophils and monocyte/macrophages. A macrophage submesothelial stratum has been suggested to constitute the first line of peritoneal defense. We have tested whether intraperitoneally administered GM-CSF could increase the number and activation of peritoneal macrophages in peritoneal dialysis patients. Eight stable patients injected 17 micrograms of GM-CSF in each of their four daily CAPD bags over three days. The clinical status, the peritoneal effluent and peripheral blood cell count, membrane receptor expression, phagocytosis activity and cytokine levels were monitored at days 0, 1, 3, 10 and 28. GM-CSF administration caused a large increase in peritoneal macrophage number (89-fold mean increase after 72 hr), returning to baseline seven days after withdrawal. GM-CSF triggered an increase in the expression of CD11b/CD18 (CR3) and its counterreceptor CD54, indicating the cellular progression into a more activated state. Both the number of phagocytic cells (55 +/- 15% to 83 +/- 10%, P < 0.05) and the phagocytic index (137 +/- 29 to 255 +/- 61, P < 0.01) were also augmented. Peritoneal effluent cytokine-chemokine levels demonstrated an increase in IL-6 and MCP-1 levels while TNF-alpha, IL-1, IL-8, MIP-1 alpha and RANTES were not significantly altered. GM-CSF administration did not affect the peritoneal transport of water or solutes. Minor side-effects were registered in two patients. In conclusion, intraperitoneal GM-CSF causes a marked and transient recruitment of primed macrophages into the peritoneum without inducing inflammatory parameters. GM-CSF should improve the peritoneal defensive capacity through potentiation of the effector functions of resident and newly-recruited macrophages.