G-CSF treatment prevents cyclophosphamide acceleration of autoimmune diabetes in the NOD mouse

J Autoimmun. 2005 Mar;24(2):125-34. doi: 10.1016/j.jaut.2005.01.001.


Cyclophosphamide (CY) accelerates autoimmune diabetes in the NOD mouse at different levels, including critical targeting of a regulatory T cell subset, exacerbation of pro-Th1 IFN-gamma production and promotion of inflammation in pancreatic islets. Here we evaluated the ability of G-CSF to antagonize the acceleration of the disease induced by CY. Human recombinant G-CSF, administered daily at 200 microg/kg by s.c. injection, protected NOD mice from CY-accelerated onset of glycosuria and insulitis. G-CSF accelerated the recovery of the T cell compartment after the depletion of the lymphoid compartment triggered by CY injection. It selectively prevented the loss of the immunoregulatory T cells expressing the CD4(+)CD25+ phenotype that also stained CD62L+ in peripancreatic lymph nodes and promoted their expansion in the spleen. In addition to this, it abrogated the robust cytokine--particularly IFN-gamma- and chemokine burst triggered in immune cells by CY. G-CSF promoted only slight changes in the inflammatory effects of CY at the target tissue site, assessed by chemokine induction within the pancreas. Thus the immunoregulatory properties of G-CSF were critical in the early control of the accelerating effects of CY on autoimmune diabetes in the NOD mouse.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, CD / immunology
  • B-Lymphocytes / cytology
  • B-Lymphocytes / drug effects
  • CD4-Positive T-Lymphocytes / drug effects
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / metabolism
  • Chemokines / biosynthesis
  • Chemokines / genetics
  • Chemokines / metabolism
  • Cyclophosphamide / antagonists & inhibitors*
  • Cyclophosphamide / pharmacology*
  • Cytokines / biosynthesis
  • Cytokines / metabolism
  • Diabetes Mellitus, Type 1 / chemically induced*
  • Diabetes Mellitus, Type 1 / complications
  • Diabetes Mellitus, Type 1 / immunology
  • Diabetes Mellitus, Type 1 / pathology*
  • Disease Progression
  • Granulocyte Colony-Stimulating Factor / pharmacology*
  • Lymphocyte Count
  • Male
  • Mice
  • Mice, Inbred NOD
  • Myeloid Cells / cytology
  • Myeloid Cells / drug effects
  • Pancreas / drug effects
  • Pancreas / metabolism
  • RNA, Messenger / genetics


  • Antigens, CD
  • Chemokines
  • Cytokines
  • RNA, Messenger
  • Granulocyte Colony-Stimulating Factor
  • Cyclophosphamide