Newly Identified Cytokine Blocks Inflammatory Bowel Disease in Mouse Model

A recently identified cytokine, interleukin 37 (IL-37) was found to prevent the development of inflammatory bowel disease (colitis) in a mouse model.

Basing their work on previous findings that IL-37 functioned as a fundamental inhibitor of innate immunity and inflammation, investigators at the University of California, San Diego (USA) and their colleagues at the University of Colorado (Boulder, USA) examined a role for IL-37 during experimental colitis.

For this study, they genetically engineered a transgenic mouse strain that expressed human IL-37 (hIL-37tg). These mice and a matching wild type population were subjected to dextran sulfate sodium (DSS)-induced colitis.

Results published in the August 22, 2011, online edition of the journal Proceedings of the [US] National Academy of Sciences revealed that during the development of colitis, clinical disease scores were reduced by 50%, and histological indices of colitis were one-third less in hIL-37tg mice compared with wild type counterparts. Reduced inflammation was associated with decreased leukocyte recruitment into the thin layer of loose connective tissue that lies beneath the colonic epithelium (lamina propria). In addition, release of IL-1beta and TNFalpha (tumor necrotic factor) from colonic explant tissue was decreased five- and 13-fold, respectively, compared with wild type mice, whereas IL-10 was increased six-fold. IL-10 was not required for the anti-inflammatory effects of IL-37, since IL-10-receptor antibody blockade did not reverse IL-37-mediated protection.

Senior author Dr. Jesus Rivera-Nieves, professor of gastroenterology at the University of California, San Diego, said, “While we still do not understand its mechanism of action, our hope is that, in the future, scientists may be able to engineer cells to overproduce IL-37 and use it to treat or control an overactive immune system in humans.”

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University of California, San Diego
University of Colorado