Regulation of T helper type-1 immunity in hapten-induced colitis by host pretreatment with granulocyte colony-stimulating factor.
Recombinant human granulocyte colony-stimulating factor (rhG-CSF) is an immunoregulatory drug whose effects include modulation of antigen-presentation. We investigated the potential ameliorative effect of pretreatment with rhG-CSF in a hapten-induced colitis animal model. Sprague-Dawley rats were given rhG-CSF (125 microg/kg subcutaneously twice a day for 5 days) before a colonic instillation of 2,4,6-trinitrobenzene sulfonic acid (TNBS) in 50% ethanol. Consequent colonic damage was evaluated pathologically, and cytokine mRNA expression levels in macroscopically inflamed sites were measured by real-time quantitative reverse transcription-polymerase chain reaction. Pretreatment with rhG-CSF remarkably attenuated both the loss of body weight and colonic wall thickening due to progressive transmural inflammation. In the control, treatment with TNBS led to a statistically significant (p < 0.05) upregulation of IFN-gamma mRNA expression in the inflammatory sites measured at post-treatment day 7. In the experimental group, pretreatment with rhG-CSF abrogated transcription of IFN-gamma (p < 0.05), but was not, however, associated with an upregulation of IL-4 or the regulatory cytokines TGF-beta and IL-10. Furthermore, transcription of IL-12p35 (a rate-limiting factor for the production of IL-12) was significantly (p < 0.05) downregulated by rhG-CSF at 24h post-TNBS instillation, whereas IL-12p40 was not affected. Pretreatment with rhG-CSF drastically attenuated the degree of TNBS-induced colitis through selective downregulation of Th1-associated cytokines.
Egi
Hiroyuki
H
Department of Surgery, Division of Frontier Medical Science, Graduate School of Biomedical Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan.
Hayamizu
Keisuke
K
Yoshimitsu
Masanori
M
Shimamoto
Fumio
F
Oishi
Koichi
K
Ohmori
Ichiro
I
Okajima
Masazumi
M
Asahara
Toshimasa
T
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D003092:Colitis / Q000188:drug therapy* / Q000276:immunology; D003106:Colon / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D016207:Cytokines / Q000187:drug effects; D005786:Gene Expression Regulation; D016179:Granulocyte Colony-Stimulating Factor / Q000235:genetics / Q000494:pharmacology*; D006801:Humans; D008297:Male; D012333:RNA, Messenger / Q000187:drug effects; D051381:Rats; D011994:Recombinant Proteins; D006377:T-Lymphocytes, Helper-Inducer / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D018417:Th1 Cells / Q000187:drug effects; D018418:Th2 Cells / Q000187:drug effects; D019282:Wasting Syndrome / Q000188:drug therapy
D000276:Adjuvants, Immunologic; D016207:Cytokines; D012333:RNA, Messenger; D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor