@article {Videla854, author = {Sebasti{\'a}n Videla and Ana Garc{\'\i}a-Lafuente and Mar{\'\i}a Antol{\'\i}n and Jaime Vilaseca and Francisco Guarner and Ernesto Crespo and Guadalupe Gonz{\'a}lez and Antonio Salas and Juan R. Malagelada}, title = {Antitumor Necrosis Factor Therapy in Rat Chronic Granulomatous Colitis: Critical Dose-Timing Effects on Outcome}, volume = {287}, number = {3}, pages = {854--859}, year = {1998}, publisher = {American Society for Pharmacology and Experimental Therapeutics}, abstract = {Inhibition of tumor necrosis fact (TNFα) is of potential benefit in the treatment of chronic inflammatory conditions. However, TNFα plays an important role in host defenses against infection, and blocking TNFα production may also have adverse effects. We tested the efficacy and safety of anti-TNFα therapy in experimental colitis induced by trinitrobenzenesulfonic acid. We cultured colonic wall specimens for bacterial growth and measured native TNFα protein synthesis in colonic tissue at days 0, 1, 4, 10 and 18 after induction of colitis. Anti-TNFα therapy (monoclonal g1 immunoglobulin, 15 mg/kg i.p., every third day) was started on either day 4 or day 10 after induction of colitis. On day 18, we measured the release of inflammatory mediators and scored colonic lesions. In acute lesions, several species of the common flora were grown, including Streptococcus, Staphylococcus, Bacteroides, clostridia and enterobacteria. In chronic lesions, only enterobacteria, clostridia and lactobacilli were isolated. TNFα production by inflamed colonic tissue was increased in both acute and chronic lesions. Anti-TNFα therapy induced a significant decrease in the release of inflammatory mediators and histopathological remission when treatment started on day 10. However, anti-TNFα therapy increased eicosanoid release and lesion scores when treatment started on day 4. In conclusion, acute colonic lesions showed polymicrobial infection. Anti-TNFα therapy induced remission of chronic intestinal inflammation, but early treatment did not prove effective. The American Society for Pharmacology and Experimental Therapeutics}, issn = {0022-3565}, URL = {https://jpet.aspetjournals.org/content/287/3/854}, eprint = {https://jpet.aspetjournals.org/content/287/3/854.full.pdf}, journal = {Journal of Pharmacology and Experimental Therapeutics} }