Increased mucosal production of granulocyte colony-stimulating factor is related to a delay in neutrophil apoptosis in Inflammatory Bowel disease

J Gastroenterol Hepatol. 1999 Jan;14(1):46-53. doi: 10.1046/j.1440-1746.1999.01807.x.


Tissue accumulation of polymorphonuclear neutrophils (PMN) in Inflammatory Bowel disease (IBD) might be, in part, due to a delay in apoptotic processes associated with the effects of their specific growth factors and inflammatory cytokines. We addressed this hypothesis by examining the activity of granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage CSF (GM-CSF) in the organ culture supernatants of colonic mucosal specimens and their regulatory effects on PMN apoptosis in patients with IBD. The contents of G-CSF and GM-CSF in the supernatants were measured by the enzyme-linked immunosorbent assays and PMN apoptosis was evaluated by acridine orange/ethidium bromide staining, respectively. Mucosal specimens obtained from patients with active IBD exhibited higher levels of G-CSF and GM-CSF activity than controls. Notably, the levels of G-CSF activity were approximately 1000-fold higher than those of GM-CSF activity. Freshly isolated PMN showed a time-related increase in the proportion of cells with characteristic features of apoptosis when they were incubated with the culture medium alone and exposure of PMN to recombinant G-CSF and GM-CSF caused a concentration-dependent inhibition of apoptosis. Incubation of PMN with the supernatants from patients with active IBD induced an inhibitory effect on PMN apoptosis; this effect was abrogated to a significant degree by pre-incubation of the supernatants with anti-G-CSF serum. This study suggests that PMN apoptosis may be delayed under the influence of soluble mediators, especially G-CSF, in the microenvironment of IBD-affected mucosa, thus providing possible mechanisms for tissue accumulation of PMN in IBD.

MeSH terms

  • Acridine Orange / metabolism
  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Apoptosis*
  • Culture Media, Conditioned / pharmacology
  • Culture Techniques
  • Cytokines / pharmacology
  • Ethidium / metabolism
  • Female
  • Granulocyte Colony-Stimulating Factor / metabolism*
  • Granulocyte-Macrophage Colony-Stimulating Factor / metabolism
  • Humans
  • Inflammatory Bowel Diseases / metabolism
  • Inflammatory Bowel Diseases / pathology*
  • Intestinal Mucosa / metabolism*
  • Intestinal Mucosa / pathology*
  • Male
  • Middle Aged
  • Neutrophils / cytology*
  • Neutrophils / drug effects


  • Culture Media, Conditioned
  • Cytokines
  • Granulocyte Colony-Stimulating Factor
  • Granulocyte-Macrophage Colony-Stimulating Factor
  • Ethidium
  • Acridine Orange