Recombinant human granulocyte colony-stimulating factor reduces colonic epithelial cell apoptosis and ameliorates murine dextran sulfate sodium-induced colitis.
OBJECTIVE
Recombinant human granulocyte colony-stimulating factor (rhG-CSF) is a potentially effective therapy for Crohn's disease. The purpose of this study was to test the rhG-CSF in murine dextran sulfate sodium-induced colitis (DSS colitis).


METHODS
Murine colitis was induced by feeding with water containing 3% DSS for 9 days. Six to 7-week-old female BALB/c mice were given rhG-CSF (100 microg/kg) or phosphate-buffered saline (PBS) subcutaneously once a day from day 0 to day 8, and the mice were sacrificed at days 3, 5, 7 and 9. Tissue specimens from the transverse colon, descending colon and rectum were obtained and stained with hematoxylin and eosin. Inflammation was scored for severity, extent, epithelial damage and crypt loss. TUNEL staining was performed to assess epithelial cell apoptosis.


RESULTS
Treatment with rhG-CSF significantly attenuated body-weight loss, stool score and shortening of the colon length in comparison with treatment with PBS (p<0.01,<0.05,<0.01, respectively). Histological scores for inflammation, epithelial cell damage and crypt loss of the rectum were less severe at day 9 in the rhG-CSF group than in the PBS group (p<0.01, 0.05, 0.01, respectively). The number of TUNEL-positive cells in the rectum was smaller in the rhG-CSF group than in the PBS group (p<0.001).


CONCLUSIONS
Treatment with rhG-CSF ameliorates murine DSS colitis by suppressing mucosal inflammation and epithelial damage in the rectum. The prevention of epithelial cell apoptosis seems to precede the anti-inflammatory action of rhG-CSF.
Department of Medicine, Graduate School of Medical Sciences, Kyusyu University, Fukuoka, Japan. t-kudo@intmed2.med.kyushu-u.ac.jp
Tetsuji
T
Kudo
Takayuki
T
Matsumoto
Ikuo
I
Nakamichi
Shinichiro
S
Yada
Motohiro
M
Esaki
Yukihiko
Y
Jo
Yutaka
Y
Ohji
Takashi
T
Yao
Mitsuo
M
Iida
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001835:Body Weight / Q000187:drug effects; D003092:Colitis / Q000139:chemically induced / Q000473:pathology*; D003106:Colon / Q000187:drug effects / Q000473:pathology*; D016264:Dextran Sulfate; D004848:Epithelium / Q000187:drug effects / Q000473:pathology; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D020287:In Situ Nick-End Labeling; D007249:Inflammation; D007413:Intestinal Mucosa / Q000187:drug effects / Q000473:pathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D011994:Recombinant Proteins
D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; D016264:Dextran Sulfate