The opioid antagonist naltrexone improves murine inflammatory bowel disease

Gail L. Matters, John F. Harms, Christopher McGovern, Leo Fitzpatrick, Anuj Parikh, Nicholas Nilo, Jill P. Smith

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Inflammatory bowel disease (IBD) is a condition of the intestine with significant morbidity. Although hereditary, environmental, immunologic, and bacterial factors have been implicated, the etiology of IBD remains unknown. Since opioid peptides modulate inflammatory cytokine production and opioid antagonists promote tissue growth and repair, we hypothesized the opioid antagonist naltrexone could reduce inflammation of the bowel. Using a chemically-induced mouse model of IBD, C57BL/6J mice received either untreated drinking water or water containing 2% dextran sulfate sodium (DSS) in two parallel regimens modeling moderate and severe colitis. After colitis was established, animals in the moderate colitis study were administered either saline (control) or naltrexone (NTX; 8 or 400 μ g/kg) daily, while those in the severe colitis study received 0.1 or 10 mg/kg NTX. DSS-treated animals had significant weight loss (p = 0.006) and higher disease activity index (DAI) scores (p < 0.001) compared to water controls. However, NTX treatment of mice with moderate colitis resulted in less weight loss, lower DAI scores, and less histologic evidence of inflammation compared to controls. Significantly, elevated levels of colonic RNA for pro-inflammatory cytokines interleukin (IL)-6 and IL-12 were also decreased toward normal with NTX. Similar to patients with severe and unresponsive disease, animals in the severe colitis study did not significantly respond to treatment. Thus, NTX therapy reverses physical symptoms, histologic evidence, and molecular markers of inflammation in moderate colitis. The mechanism by which NTX acts to reverse colitis is related in part to the decreased expression of pro-inflammatory cytokines.

Original languageEnglish (US)
Pages (from-to)179-187
Number of pages9
JournalJournal of Immunotoxicology
Volume5
Issue number2
DOIs
StatePublished - Apr 1 2008

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Naltrexone
Narcotic Antagonists
Colitis
Inflammatory Bowel Diseases
Dextran Sulfate
Animals
Cytokines
Inflammation
Weight Loss
Opioid Peptides
Water
Interleukin-12
Drinking Water
Animal Diseases
Interleukin-6
Immunologic Factors
Repair
Inbred C57BL Mouse
RNA
Tissue

All Science Journal Classification (ASJC) codes

  • Immunology
  • Toxicology

Cite this

Matters, G. L., Harms, J. F., McGovern, C., Fitzpatrick, L., Parikh, A., Nilo, N., & Smith, J. P. (2008). The opioid antagonist naltrexone improves murine inflammatory bowel disease. Journal of Immunotoxicology, 5(2), 179-187. https://doi.org/10.1080/15476910802131469
Matters, Gail L. ; Harms, John F. ; McGovern, Christopher ; Fitzpatrick, Leo ; Parikh, Anuj ; Nilo, Nicholas ; Smith, Jill P. / The opioid antagonist naltrexone improves murine inflammatory bowel disease. In: Journal of Immunotoxicology. 2008 ; Vol. 5, No. 2. pp. 179-187.
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Matters, GL, Harms, JF, McGovern, C, Fitzpatrick, L, Parikh, A, Nilo, N & Smith, JP 2008, 'The opioid antagonist naltrexone improves murine inflammatory bowel disease', Journal of Immunotoxicology, vol. 5, no. 2, pp. 179-187. https://doi.org/10.1080/15476910802131469

The opioid antagonist naltrexone improves murine inflammatory bowel disease. / Matters, Gail L.; Harms, John F.; McGovern, Christopher; Fitzpatrick, Leo; Parikh, Anuj; Nilo, Nicholas; Smith, Jill P.

In: Journal of Immunotoxicology, Vol. 5, No. 2, 01.04.2008, p. 179-187.

Research output: Contribution to journalArticle

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T1 - The opioid antagonist naltrexone improves murine inflammatory bowel disease

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