Abstract |
Gliotoxin is a fungal metabolite that has immunosuppressive properties. First, we determined if gliotoxin could inhibit cytokine production from macrophage and colonic epithelial cell lines, as well as whether it inhibited nuclear factor-kappa B in these same cell types. Second, we evaluated whether gliotoxin could reduce dextran sodium sulfate-induced colitis in rats. A disease activity index, myeloperoxidase activity, and cytokine levels were evaluated on either day 7 or 21. In both cell lines, gliotoxin dose dependently inhibited cytokine production and nuclear factor-kappa B. On day 21, gliotoxin significantly reduced disease activity ( diarrhea and bloody stools) in rats. On day 7, gliotoxin treatment significantly improved various indices of colitis, including colonic cytokine levels. Decreased food consumption and weight gain was evident with a larger dose of gliotoxin. In summary, gliotoxin, a nuclear factor-kappa B inhibitor, effectively reduced dextran sodium sulfate-induced colitis in rats. However, gliotoxin exhibited a narrow therapeutic to toxicity ratio in these rats.
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Authors | L R Fitzpatrick, J Wang, T Le |
Journal | Digestive diseases and sciences
(Dig Dis Sci)
Vol. 45
Issue 12
Pg. 2327-36
(Dec 2000)
ISSN: 0163-2116 [Print] United States |
PMID | 11258552
(Publication Type: Journal Article)
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Chemical References |
- Immunosuppressive Agents
- Interleukin-1
- Interleukin-1beta
- NF-kappa B
- Peptide Fragments
- Tumor Necrosis Factor-alpha
- interleukin-1beta (163-171)
- Gliotoxin
- Dextran Sulfate
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Topics |
- Animals
- Cell Line
- Colitis
(chemically induced, drug therapy)
- Dextran Sulfate
- Epithelial Cells
(immunology)
- Gliotoxin
(pharmacology, therapeutic use)
- Humans
- Immunosuppressive Agents
(pharmacology, therapeutic use)
- Interleukin-1
(biosynthesis)
- Interleukin-1beta
- Macrophages
(immunology)
- Male
- NF-kappa B
(biosynthesis)
- Peptide Fragments
(biosynthesis)
- Rats
- Rats, Wistar
- Tumor Necrosis Factor-alpha
(biosynthesis)
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