ORIGINAL ARTICLE Are sTWEAK and IL-17A Levels in Inflammatory Bowel Disease Associated with Disease Activity and Etiopathogenesis? Mustafa Kaplan, MD,* Mahmut Yuksel, MD,* Ihsan Ates, MD, † Zeki Mesut Yalın Kilic, MD,* Hasan Kilic, MD, ‡ Hale Ates, MD, § and Ertugrul Kayacetin, MD* Background: We aimed to identify the levels of soluble tumor necrosis factor-like weak inducer of apoptosis (sTWEAK) and interleukin 17A (IL-17A) in inflammatory bowel disease (IBD) and to examine their relationship with disease activity. Methods: A total of 92 patients with IBD, in which 54 patients were diagnosed with ulcerative colitis and 38 patients with Crohn’s disease (CD), and 104 healthy controls were included in the study. The Rachmilewitz endoscopic activity index was calculated in ulcerative colitis, and the CD activity index was calculated in CD. Results: sTWEAK (P , 0.001) and IL-17A (P ¼ 0.006) levels were higher in the IBD group than in the control group. Both in the IBD group and ulcerative colitis and CD subgroups, in active patients, sTWEAK and IL-17A levels were found to be higher than in inactive and control groups. In the IBD group, a positive correlation was determined between sTWEAK and IL-17A, and C-reactive protein, endoscopic activity index, and CD activity index. In multivariable regression analysis, C-reactive protein and sTWEAK levels were determined to be an independent risk factor for both endoscopic activity index and CD activity index. In receiver operating curve analysis, the sTWEAK level was determined to predict IBD with high sensitivity and specificity with a value of .588.34 pg/mL and activity with a value of .669.28 pg/mL. Conclusion: Based on these results, we ascertain that sTWEAK has a role in etiopathogenesis of IBD. In addition, we believe that sTWEAK could be used as a marker for both disease activity criteria and treatment monitoring. (Inflamm Bowel Dis 2016;22:615–622) Key Words: chronic inflammation, Crohn’s disease, proinflammatory cytokines, T helper-17, ulcerative colitis I nflammatory bowel disease (IBD) is a chronic IBD characterized by remission and relapses. It is divided into 2 main subgroups: ulcerative colitis (UC), which generally affects the colon and inflammation is generally limited to the mucosa and submucosa, and Crohn’s disease (CD), which is characterized by transmural and skip lesions that can affect the entire digestive tract from the mouth to the anus. 1,2 Although risk factors that influence the eti- ology of IBD are not clear, besides environmental, genetic, micro- bial, and familial factors, immunity also is believed to be a factor that affects the etiology. 3 Of note, the increase in proinflammatory activity of T lymphocytes has been shown to play a dominant role in the immunity against IBD. 4 Among proinflammatory T lympho- cytes, best identified ones are T helper 1 (Th1), T helper 2 (Th2), and T helper 17 (Th17). 5 Th1 lymphocytes mainly secrete inter- leukin 1 (IL-1), interleukin 2 (IL-2), and tumor necrosis factor (TNF); Th2 lymphocytes secrete interleukin 4 (IL-4), interleukin 5 (IL-5), and interleukin 13 (IL-13); and Th17 secretes interleukin 17 (IL-17). 6,7 Recently, the relationship between inflammatory dis- eases and TNF subgroups and proinflammatory subgroups such as IL-17 is often being emphasized. 8–10 Tumor necrosis factor-like weak inducer of apoptosis (TWEAK), being a cytokine from the TNF superfamily, shows its activity through fibroblast growth factor-inducible 14 (Fn14) receptor. 11 TWEAK shows activity at a cellular level with membrane-bound mTWEAK and its soluble form, soluble tumor necrosis factor-like weak inducer of apoptosis (sTWEAK). 12 sTWEAK-Fn14 complex shows biological activities such as cell differentiation, apoptosis, atherosclerosis, and inflammation through the nuclear factor kB (NF-kB) pathway. 13 Although IL-17 is mainly secreted by Th17, it is shown to be synthesized by macrophages, natural killer T cells, dendritic cells, microglia, neutrophils, eosinophil, and gd T cells as well. 14 There are 6 forms of interleukin (IL)-17 (IL-17 A–F) in total, among which IL-17A is the primary active form. In inflammatory incidents, IL-17 plays a role in activation and migration of neutrophils. 15 In the literature review, we could not find sufficient number of studies on the role of sTWEAK and IL-17A in Received for publication August 31, 2015; Accepted September 14, 2015. From the *Department of Gastroenterology, Turkey Yuksek Ihtisas Training and Research Hospital, Ankara, Turkey; † Department of Internal Medicine, Ankara Nu- mune Training and Research Hospital, Ankara, Turkey; ‡ Department of Microbiol- ogy, Turkey Yuksek Ihtisas Training and Research Hospital, Ankara, Turkey; and § Department of Immunology and Allergy, Atatürk Chest Diseases and Thoracic Surgery Training and Research Hospital, Ankara, Turkey. The authors have no conflict of interest to disclose. Reprints: Ihsan Ates, MD, Department of Internal Medicine, Ankara Numune Training and Research Hospital, 06100 Sihhiye, Ankara, Turkey (e-mail: dr.ihsanates@hotmail.com). Copyright © 2015 Crohn’s & Colitis Foundation of America, Inc. DOI 10.1097/MIB.0000000000000632 Published online 9 December 2015. Inflamm Bowel Dis  Volume 22, Number 3, March 2016 www.ibdjournal.org | 615 ’ Copyright © 2015 Crohn’s & Colitis Foundation of America, Inc. Unauthorized reproduction of this article is prohibited. Downloaded from https://academic.oup.com/ibdjournal/article-abstract/22/3/615/4561771 by guest on 28 June 2020