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

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 proin...

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Veröffentlicht in:Tohoku journal of experimental medicine 2015-02, Vol.235 (2), p.127-134
Hauptverfasser: Yaoita, Takao, Sasaki, Yu, Yokozawa, Junji, Sato, Takeshi, Kanno, Nana, Sakuta, Kazuhiro, Yagi, Makoto, Yoshizawa, Kazuya, Iwano, Daisuke, Nagino, Ko, Nomura, Eiki, Abe, Yasuhiko, Nishise, Shoichi, Takeda, Hiroaki, Kawata, Sumio, Ueno, Yoshiyuki
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container_issue 2
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container_title Tohoku journal of experimental medicine
container_volume 235
creator Yaoita, Takao
Sasaki, Yu
Yokozawa, Junji
Sato, Takeshi
Kanno, Nana
Sakuta, Kazuhiro
Yagi, Makoto
Yoshizawa, Kazuya
Iwano, Daisuke
Nagino, Ko
Nomura, Eiki
Abe, Yasuhiko
Nishise, Shoichi
Takeda, Hiroaki
Kawata, Sumio
Ueno, Yoshiyuki
description 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-Apc(Min/+) 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 Apc(Min/+) mice fed the high-fat diet. We suggest that IL-6 signaling may be responsible for the obesity-associated colorectal tumorigenesis.
doi_str_mv 10.1620/tjem.235.127
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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-Apc(Min/+) 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 Apc(Min/+) mice fed the high-fat diet. 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subjects Adenomatous Polyposis Coli - genetics
Animals
Antibodies - administration & dosage
Antibodies - pharmacology
Antibodies - therapeutic use
Blood Glucose - metabolism
Diet, High-Fat
Female
Insulin - blood
Intestinal Polyps - blood
Intestinal Polyps - drug therapy
Male
Mice, Inbred C57BL
Rats
Receptors, Interleukin-6 - immunology
Triglycerides - blood
title Treatment with anti-interleukin-6 receptor antibody ameliorates intestinal polyposis in Apc(Min/+) mice under high-fat diet conditions
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