Treatment with anti-interleukin-6 receptor antibody ameliorates intestinal polyposis in ApcMin/+ mice under high-fat diet conditions

  • Yaoita Takao
    Department of Gastroenterology, Yamagata University Faculty of Medicine
  • Sasaki Yu
    Department of Gastroenterology, Yamagata University Faculty of Medicine
  • Yokozawa Junji
    Department of Integrative Genomics, Tohoku Medical Megabank Organization
  • Sato Takeshi
    Department of Gastroenterology, Yamagata University Faculty of Medicine Division of Endoscopy, Yamagata University Hospital
  • Kanno Nana
    Department of Gastroenterology, Yamagata University Faculty of Medicine
  • Sakuta Kazuhiro
    Department of Gastroenterology, Yamagata University Faculty of Medicine
  • Yagi Makoto
    Department of Gastroenterology, Yamagata University Faculty of Medicine
  • Yoshizawa Kazuya
    Department of Gastroenterology, Yamagata University Faculty of Medicine
  • Iwano Daisuke
    Department of Gastroenterology, Yamagata University Faculty of Medicine
  • Nagino Ko
    Yamagata City Hospital Saiseikan
  • Nomura Eiki
    Department of Gastroenterology, Yamagata University Faculty of Medicine
  • Abe Yasuhiko
    Department of Gastroenterology, Yamagata University Faculty of Medicine
  • Nishise Shoichi
    Department of Gastroenterology, Yamagata University Faculty of Medicine
  • Takeda Hiroaki
    Department of Gastroenteorogy, Yamagata Prefectural Central Hospital
  • Kawata Sumio
    Hyogo Prefectural Nishinomiya Hospital
  • Ueno Yoshiyuki
    Department of Gastroenterology, Yamagata University Faculty of Medicine

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タイトル別名
  • Treatment with Anti-Interleukin-6 Receptor Antibody Ameliorates Intestinal Polyposis in <i>Apc</i><sup><i>Min/+</i></sup> Mice under High-Fat Diet Conditions

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The prevalence of colorectal malignancies is increasing in the world. The parallel increase of metabolic syndrome gives a speculation between these two conditions, although the precise mechanism is still unclear. Interleukin-6 (IL-6) is a cytokine known to correlate with obesity and serve as a proinflammatory adipokine. In the present study, we investigated the effect of IL-6 signaling blockade on intestinal polyp formation in obesity using a mouse model of adenomatous polyposis coli (Apc). Male C57BL/6J-ApcMin/+ mice were fed a high-fat diet from 5 weeks of age, and the overweight mice thus obtained were given a weekly intraperitoneal injection of anti-mouse IL-6 receptor antibody (MR16-1) from 6 to 15 weeks of age, while control mice received IgG or phosphate-buffered saline (PBS). The total number of intestinal polyps was significantly decreased in the MR16-1-injected group (53.1 ± 6.8) relative to the control groups (PBS-injected, 81.3 ± 6.1; rat IgG-injected, 74.7 ± 4.8, p = 0.01), and in particular the number of polyps larger than 2 mm in diameter was markedly decreased. In addition, the mean diameter of polyps in the MR16-1-injected group was significantly smaller than that in the control groups. On the other hand, no significant differences in body weight, epididymal fat pad mass, or the plasma levels of glucose, insulin and triglyceride were observed among the three groups. Thus, treatment with anti-IL-6 receptor antibody suppressed polyp growth in obese ApcMin/+ mice fed the high-fat diet. We suggest that IL-6 signaling may be responsible for the obesity-associated colorectal tumorigenesis.

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