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Inhibition of TNF-alpha improves indomethacin-induced enteropathy in rats by modulating iNOS expression.
- Source :
-
Digestive diseases and sciences [Dig Dis Sci] 2005 Sep; Vol. 50 (9), pp. 1677-83. - Publication Year :
- 2005
-
Abstract
- TNF-alpha, including other proinflammatory cytokines alone or in combination, induces iNOS expression and upregulates inflammatory responses. We evaluated the relationship between TNF-alpha and iNOS expression in indomethacin-induced jejunoileitis in male Sprague-Dawley rats. Rats were fed a daily dose of a phosphodiesterase inhibitor-either theophylline or pentoxifylline-for 2 days. Jejunoileitis was induced with two subcutaneous injections of indomethacin (7.5 mg/kg) 24 hr apart and theophylline or pentoxifylline continued for 12 hr or 4 days. Other rats received a single intraperitoneal injection of anti-TNF-alpha monoclonal antibody (TNF-Ab) 30-min before indomethacin. At 4 days TNF-Ab, theophylline, or pentoxifylline treatment significantly decreased indomethacin-induced ulceration, myeloperoxidase activity, and disease activity index. Although indomethacin significantly increased serum TNF-alpha and nitrate/nitrite levels over the control value as early as 12 hr, iNOS expression was detected only after 4 days. Serum IL-1beta level did not change at 12 hr but increased fourfold at 4 days. Treatment with TNF-Ab, theophylline, or pentoxifylline significantly reduced serum/tissue TNF-alpha, IL-1beta, nitrate/nitrite, and iNOS expression. The downregulation of nitrate/nitrite by these inhibitors suggests that TNF-alpha modulates iNOS expression.
- Subjects :
- Animals
Antibodies, Monoclonal
Down-Regulation
Ileitis immunology
Ileitis veterinary
Inflammation
Jejunal Diseases immunology
Jejunal Diseases veterinary
Male
Nitrates
Nitric Oxide Synthase metabolism
Nitric Oxide Synthase Type II
Nitrites
Pentoxifylline administration & dosage
Pentoxifylline pharmacology
Phosphodiesterase Inhibitors administration & dosage
Phosphodiesterase Inhibitors pharmacology
Rats
Rats, Sprague-Dawley
Theophylline administration & dosage
Theophylline pharmacology
Up-Regulation
Anti-Inflammatory Agents, Non-Steroidal pharmacology
Anti-Inflammatory Agents, Non-Steroidal toxicity
Ileitis chemically induced
Indomethacin pharmacology
Indomethacin toxicity
Jejunal Diseases chemically induced
Nitric Oxide Synthase biosynthesis
Tumor Necrosis Factor-alpha physiology
Subjects
Details
- Language :
- English
- ISSN :
- 0163-2116
- Volume :
- 50
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- Digestive diseases and sciences
- Publication Type :
- Academic Journal
- Accession number :
- 16133968
- Full Text :
- https://doi.org/10.1007/s10620-005-2914-0