title: G-CSF treatment prevents cyclophosphamide acceleration of autoimmune diabetes in the NOD mouse.
abstract: 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.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale INSERM U580, Institut de Recherche Necker Enfants Malades, Hôpital Necker, 161 rue de Sèvres, 75743 Paris Cedex 15, France.
authors.forename: Karine
authors.initials: K
authors.lastname: Hadaya
authors.forename: Hassen
authors.initials: H
authors.lastname: Kared
authors.forename: Annie
authors.initials: A
authors.lastname: Masson
authors.forename: Lucienne
authors.initials: L
authors.lastname: Chatenoud
authors.forename: Flora
authors.initials: F
authors.lastname: Zavala
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000276:immunology; D001402:B-Lymphocytes / Q000166:cytology / Q000187:drug effects; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D018925:Chemokines / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D003520:Cyclophosphamide / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D016207:Cytokines / Q000096:biosynthesis / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000139:chemically induced* / Q000150:complications / Q000276:immunology / Q000473:pathology*; D018450:Disease Progression; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D018655:Lymphocyte Count; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D022423:Myeloid Cells / Q000166:cytology / Q000187:drug effects; D010179:Pancreas / Q000187:drug effects / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics
chemical_list: D015703:Antigens, CD; D018925:Chemokines; D016207:Cytokines; D012333:RNA, Messenger; D016179:Granulocyte Colony-Stimulating Factor; D003520:Cyclophosphamide