Interleukin 37 expression protects mice from colitis

Eoin McNamee, Joanne Masterson, Paul Jedlicka, Martine McManus, Almut Grenz, Colm Collins, Marcel Nold, Claudia Nold, Philip Bufler, Charles Dinarello, Jesus Rivera-Nieves

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291 Citations (Scopus)

Abstract

IL-37, a newly described member of the IL-1 family, functions as a fundamental inhibitor of innate inflammation and immunity. In the present study, we examined a role for IL-37 during experimental colitis. A transgenic mouse strain was generated to express human IL-37 (hIL-37tg), and these mice were subjected to dextran sulfate sodium (DSS)-induced colitis. Despite the presence of a CMV promoter to drive expression of IL-37, mRNA transcripts were not present in colons at the resting state. Expression was observed only upon disruption of the epithelial barrier, with a six- to sevenfold increase (P = 0.02) on days 3 and 5 after continuous exposure to DSS. During the development of colitis, clinical disease scores were reduced by 50 (P <0.001), and histological indices of colitis were one-third less in hIL-37tg mice compared with WT counterparts (P <0.001). Reduced inflammation was associated with decreased leukocyte recruitment into the colonic lamina propria. In addition, release of IL-1beta and TNFalpha from ex vivo colonic explant tissue was decreased 5- and 13-fold, respectively, compared with WT (P
Original languageEnglish
Pages (from-to)16711 - 16716
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume108
Issue number40
DOIs
Publication statusPublished - 2011

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