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An immuno-blocking agent targeting IL-1β and IL-17A reduces the lesion of DSS-induced ulcerative colitis in mice

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Abstract

In recent decades when biological agents have flourished, a part of patients suffering from inflammatory bowel disease (IBD) have received the treatment of tumor necrosis factor inhibitors or IL-1 antibodies. This study aims to investigate the anti-colitis effects of bispecific antibody (FL-BsAb1/17) targeting IL-1β and IL-17A comparing with TNF-α soluble receptor medicine etanercept. IBD model in mice was established by drinking 3% DSS (dextran sulfate sodium salt). On the first day of drinking DSS, treatments with etanercept (5 mg/kg) or different doses of FL-BsAb1/17 (1 mg/kg, 5 mg/kg, and 10 mg/kg) were started by intraperitoneal injection every other day. The results demonstrated that FL-BsAb1/17 treatment was more effective than etanercept at the same dose (5 mg/kg) in relieving the typical symptom of ulcerative colitis induced by DSS (such as the severity score and intestinal shortening), and down-regulating the expression of inflammatory factors (IL-17A, IL-6, IL-12, IL-22, IL-1β, IL-23, TNF-α) in the serum and colon. FL-BsAb1/17 could also reduce the degree of intestinal fibrosis. The same dose of FL-BsAb1/17 (5 mg/kg) performed better than etanercept in down-regulating MDA and up-regulating SOD (superoxide dismutase), CAT (catalase), and T-AOC (total antioxidant capacity) in serum. Both FL-BsAb1/17 and etanercept could reduce the transcription of Bax and increase the transcription of Bcl-2 and slow down apoptosis in colitis colon tissue. We conclude that the blocking of IL-1β and IL-17A can inhibit DSS-induced ulcerative colitis and FL-BsAb1/17 may have potential to become a new dual-target candidate for colitis treatment.

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Funding

This work was supported by the National Key R&D Program of China (grant numbers: 2017YFD0501004, 2017YFD0501102) and National Natural Science Foundation of China (31600740).

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Authors and Affiliations

  1. Bio-pharmaceutical Lab, College of Life Sciences, Northeast Agricultural University, Harbin, 150030, Heilongjiang, China

    Qi Yin, Xuelei Pi, Guiping Ren, Zhihang Liu, Han Liu, Mengxia Wang, Wenying Sun, Siyu Li, Deshan Li & Jiechao Yin

  2. Harbin Pharmaceutical Group R&D Center, Harbin, 150025, Heilongjiang, China

    Yuanyuan Jiang

  3. Key Laboratory of Agricultural Biological Functional Gene, Harbin, 150030, Heilongjiang, China

    Guiping Ren, Deshan Li & Jiechao Yin

  4. School of Pharmacy, Yancheng Teachers University, Xiwang Road, Yancheng, 22400, Jiangsu, China

    Zhenqiu Gao

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  1. Qi Yin
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Correspondence to Jiechao Yin.

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Yin, Q., Pi, X., Jiang, Y. et al. An immuno-blocking agent targeting IL-1β and IL-17A reduces the lesion of DSS-induced ulcerative colitis in mice. Inflammation 44, 1724–1736 (2021). https://doi.org/10.1007/s10753-021-01449-4

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