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Effects of retinoids in mouse models of colitis: benefit or danger to the gastrointestinal tract?


Frey-Wagner, Isabelle; Fischbeck, Anne; Cee, Alexandra; Leonardi, Irina; Gruber, Sven; Becker, Eugenia; Atrott, Kirstin; Lang, Silvia; Rogler, Gerhard (2013). Effects of retinoids in mouse models of colitis: benefit or danger to the gastrointestinal tract? Inflammatory Bowel Diseases, 19(11):2356-2365.

Abstract

BACKGROUND: In vitro and in vivo data have shown that retinoid treatment promotes an anti-inflammatory milieu with few adverse effects toward the gastrointestinal tract. The in vivo studies reported here further evaluate retinoid effects in 2 mouse models of inflammatory bowel disease. METHOD: Chronic dextran sulfate sodium colitis was induced in age- and weight-matched C57Bl/6 mice by 4 cycles of dextran sulfate sodium administration (6-8 animals/group). At cycle 4, animals were administered 13-cis-retinoic acid (isotretinoin, 30 mg/kg) or vehicle (oral gavage) or 4-oxo-13-cis-retinoic acid (15 mg/kg, intraperitoneal) daily. T-cell transfer colitis was induced in CB17 SCID mice by transfer of naive CD4CD62L T cells and treated by transfer of regulatory CD4CD25 T cells (4-6 animals/group); isolated from BALB/c mice after treatment with isotretinoin or vehicle, as above, for 2 weeks. Assessments included endoscopic and histological scores, myeloperoxidase activity, serum cytokines, and plasma isotretinoin levels. RESULTS: Retinoid-treated animals with colitis showed comparable changes in myeloperoxidase activity, and endoscopic and histological scores, versus untreated animals with colitis. Modest and comparable changes were seen in body weight and colon length in animals injected with naive T cells from isotretinoin-treated donors versus those injected with T cells from vehicle-treated donors. Retinoid treatment was consistently associated with lower interleukin-12 levels, which, after the transfer of naive T cells from isotretinoin-treated donors, supported isotretinoin-mediated predisposition of naive T cells toward reduced proinflammatory cytokine expression. Colitis had no effect on isotretinoin exposure. CONCLUSIONS: Retinoids attenuate the proinflammatory cytokine response in vivo, with only modest effects on body weight and parameters of gastrointestinal morphology.

Abstract

BACKGROUND: In vitro and in vivo data have shown that retinoid treatment promotes an anti-inflammatory milieu with few adverse effects toward the gastrointestinal tract. The in vivo studies reported here further evaluate retinoid effects in 2 mouse models of inflammatory bowel disease. METHOD: Chronic dextran sulfate sodium colitis was induced in age- and weight-matched C57Bl/6 mice by 4 cycles of dextran sulfate sodium administration (6-8 animals/group). At cycle 4, animals were administered 13-cis-retinoic acid (isotretinoin, 30 mg/kg) or vehicle (oral gavage) or 4-oxo-13-cis-retinoic acid (15 mg/kg, intraperitoneal) daily. T-cell transfer colitis was induced in CB17 SCID mice by transfer of naive CD4CD62L T cells and treated by transfer of regulatory CD4CD25 T cells (4-6 animals/group); isolated from BALB/c mice after treatment with isotretinoin or vehicle, as above, for 2 weeks. Assessments included endoscopic and histological scores, myeloperoxidase activity, serum cytokines, and plasma isotretinoin levels. RESULTS: Retinoid-treated animals with colitis showed comparable changes in myeloperoxidase activity, and endoscopic and histological scores, versus untreated animals with colitis. Modest and comparable changes were seen in body weight and colon length in animals injected with naive T cells from isotretinoin-treated donors versus those injected with T cells from vehicle-treated donors. Retinoid treatment was consistently associated with lower interleukin-12 levels, which, after the transfer of naive T cells from isotretinoin-treated donors, supported isotretinoin-mediated predisposition of naive T cells toward reduced proinflammatory cytokine expression. Colitis had no effect on isotretinoin exposure. CONCLUSIONS: Retinoids attenuate the proinflammatory cytokine response in vivo, with only modest effects on body weight and parameters of gastrointestinal morphology.

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3 citations in Scopus®
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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic for Gastroenterology and Hepatology
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:2013
Deposited On:17 Oct 2013 10:09
Last Modified:07 Dec 2017 22:55
Publisher:Wiley-Blackwell
ISSN:1078-0998
Publisher DOI:https://doi.org/10.1097/MIB.0b013e31829cf1fc
PubMed ID:23899542

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