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Inhibition of TNF-α Improves Indomethacin-Induced Enteropathy in Rats by Modulating iNOS Expression

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Abstract

TNF-α, including other proinflammatory cytokines alone or in combination, induces iNOS expression and upregulates inflammatory responses. We evaluated the relationship between TNF-α 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-α 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-α and nitrate/nitrite levels over the control value as early as 12 hr, iNOS expression was detected only after 4 days. Serum IL-1β 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-α, IL-1β, nitrate/nitrite, and iNOS expression. The downregulation of nitrate/nitrite by these inhibitors suggests that TNF-α modulates iNOS expression.

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Authors and Affiliations

  1. Department of Medicine, Division of Gastroenterology, SUNY Upstate Medical University, 750 East Adams Street, Syracuse, New York, 13210, USA

    B. Saud MD, J. Nandi PhD, G. Ong MD, S. Finocchiaro BS & R. A. Levine MD

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  1. B. Saud MD
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  2. J. Nandi PhD
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  3. G. Ong MD
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  4. S. Finocchiaro BS
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  5. R. A. Levine MD
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Correspondence to R. A. Levine MD.

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Saud, B., Nandi, J., Ong, G. et al. Inhibition of TNF-α Improves Indomethacin-Induced Enteropathy in Rats by Modulating iNOS Expression. Dig Dis Sci 50, 1677–1683 (2005). https://doi.org/10.1007/s10620-005-2914-0

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  • DOI: https://doi.org/10.1007/s10620-005-2914-0

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