| Project/Area Number |
07670635
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Gastroenterology
|
|---|
| Research Institution | Kurume University |
|---|
Principal Investigator |
MITSUYAMA Keiichi Kurume University School of Medicine, 2nd Department of Medicine, Assistant, 医学部, 助手 (20200066)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
SHIRACHI Akira Kurume University School of Medicine, 2nd Department of Medicine, Assistant, 医学部, 助手 (20279152)
SAIKI Tomohisa Kurume University School of Medicine, 2nd Department of Medicine, Assistant, 医学部, 助手 (60279148)
TATEISHI Hideo Kurume University School of Medicine, 2nd Department of Medicine, Assistant, 医学部, 助手 (80258441)
|
|---|
| Project Period (FY) |
1995 – 1996
|
| Project Status |
Completed (Fiscal Year 1996)
|
| Budget Amount *help |
¥1,900,000 (Direct Cost: ¥1,900,000)
Fiscal Year 1996: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1995: ¥900,000 (Direct Cost: ¥900,000)
|
|---|
| Keywords | interleukin-10 / inflammatory bowel disease / Crohn's disease / ulcerative colitis / cytokines / dextran sulfate sodium / colitis / 実験腸炎 / 腫瘍性大腸炎 |
|---|
| Research Abstract |
To clarify the functional role of interleukin (IL) -10 in inflammatory bowel disease (IBD), following experiments were performed
A.Studies in Patients with IBD
1. Effects of IL-10 or anti-IL-10 administered on tissue cytokine production in vitro
A 24-h culture of inflamed tissues obtained from IBD patients with recombinant IL-10 significantly reduced their production of TNFalpha and IL-1beta. Blocking IL-10 in the culture using neutralizing antibodies against IL-10 resulted in a significant increase in the production of TNFalpha and IL-1beta.
B.Studies in a Murine Model of Dextran Sulfate Sodium (DSS) -Induced Colitis
1. Colonic cytokine profiles in DSS-induced colitis
During the course of DSS-induced colitis, inflammatory indices and the levels of cytokines at the sites of disease were monitored. Tumor necrosis factor (TNF) -alpha and IL-1beta peaked on day 5 and gradually declined thereafter. This profile correlated well with the histologic scores and tissue MPO levels. The IL-10 peak foll
… More
owed the peaks of TNFalpha and IL-1beta, and reached maximal levels on day 7.
2. Effects of IL-10 or anti-IL-10 administered on tissue cytokine production in vitro
A 24-h culture of normal or inflamed tissues from DSS-induced colitis with recombinant IL-10 significantly reduced their production of TNFalpha and IL-1beta. Blocking IL-10 in the culture using neutralizing antibodies against IL-10 resulted in a significant increase in the production of TNFalpha and IL-1beta.
3. Effect of IL-10 or anti-IL-10 administered on DSS-induced colitis in vivo
Treatment with recombinant IL-10 resulted in significant improvements in various inflammatory parameters, including histologic scores, colon length and rectal bleeding. In contrast, the colon length was significantly shorter in mice treated with anti-IL-10 antibodies than in those which had received control IgG.Although there was a trend towards exacerbation of other inflammatory parameters by anti-IL-10, the difference in these did not reach statistical significance.
These data suggest a potential therapeutic role for IL-10, and we encourage further clinical trials with IL-10 in patients with inflammatory bowel disease. Less
|
