Clinical Significance of Serum Thioredoxin 1 Levels in Patients with Acute Pancreatitis Shinya Ohashi, MD,* Akiyoshi Nishio, MD, PhD,* Hajime Nakamura, MD, PhD,† Masahiro Kido, MD,* Keiichi Kiriya, MD,* Masanori Asada, MD,* Hiroyuki Tamaki, MD,* Toshiro Fukui, MD,* Kimio Kawasaki, MD, PhD,* Norihiko Watanabe, MD, PhD,* Junji Yodoi, MD, PhD,‡ Kazuichi Okazaki, MD, PhD,§ and Tsutomu Chiba, MD, PhD* Objective: Thioredoxin 1 (TRX-1), a redox-regulating protein with antioxidant activity, is induced by oxidative stress, and serum TRX-1 levels are recognized as an oxidative-stress marker. The aim of this study was to clarify the clinical significance of serum TRX-1 levels in patients with acute pancreatitis (AP) and evaluate the usefulness of this measurement in assessing disease severity. Methods: Serum TRX-1 levels were determined on admission in 18 patients with severe AP and 36 patients with mild AP. We also investigated the relationship between serum TRX-1 levels and clinical and laboratory data. Results: The median serum TRX-1 levels on admission were 54.9 ng/mL in mild AP and 118.8 ng/mL in severe AP. When the cutoff value for TRX-1 in predicting severe AP was determined to be 100 ng/mL, its sensitivity, specificity, and accuracy were 83.3%, 94.4%, and 90.7%, respectively. A significant correlation was observed between serum TRX-1 levels and Ranson score (r = 0.674), C-reactive protein (r = 0.718), interleukin 6 (r = 0.712), leukocyte count (r = 0.642), and serum amylase (r = 0.436). Conclusions: Serum TRX-1 levels significantly correlate with AP severity. TRX-1 should constitute a reliable oxidative-stress marker for the evaluation of AP severity in relation to oxidative stress. Key Words: thioredoxin 1, acute pancreatitis, oxidative stress, predictive marker, reactive oxygen species (Pancreas 2006;32:264Y270) A cute pancreatitis (AP) is triggered by the premature activation of digestive enzymes within pancreatic acinar cells and the subsequent autodigestion of the pancreas, which induces an acute inflammatory reaction at the site of injury. 1 Amplified production of inflammatory mediators accelerates the progression of the disease, leading both to the aggravation of local pancreatic inflammation and to a systemic inflam- matory response. 2 Therefore, AP comprises a broad spectrum of the disease severity. Most patients with AP (approximately 80%Y85%) show a mild form of the disease with an uncomplicated course, whereas the others develop severe pancreatitis with considerable morbidity and mortality. 3 Overall, the mortality rate in patients with severe AP is 25% to 30%. 4,5 In 1992, the Atlanta criteria were proposed as an international clinical classification of AP, in which Bsevere AP[ is defined as AP with complications, including systemic organ failure, as well as local manifestations such as pancreatic necrosis, abscess, or pseudocyst. 6 Because severity assessment is crucial for the treatment of AP, several criteria have been defined to predict the severity of AP. These include clinicobiochemical scoring systems (eg, Ranson criteria, 7 modified Glasgow criteria, 8 and APACHE II criteria 9 ). How- ever, both the Ranson and modified Glasgow criteria require 48 hours for complete data collection and perform less accurately outside their index populations. 10 The accuracy of the APACHE II score on admission is useful, but its com- plicated system is inconvenient. 9 Thus, a simple and reliable predictor of outcome in the course of AP is still lacking. Recent research suggests that reactive oxygen species (ROS) are a critical factor in the pathophysiology of AP and that the oxidative stress caused by ROS is related to disease severity. 11Y13 Indeed, ROS directly cause the destruction of lipid membranes by the peroxidation of fatty acids and trigger various inflammatory processes that result in the development of complications. 14,15 Therefore, it is logical to infer that markers of oxidative stress will accurately predict the severity of AP. However, there are few clinically significant markers with which to evaluate oxidative stress in patients with AP. Thioredoxin 1 (TRX-1) is an endogenous protein that contains a redox-active disulfide/dithiol within a highly conserved active site sequence (Cys-Gly-Pro-Cys). 16 TRX-1 has a variety of biologic activities, including the scavenging of ROS and the regulation of redox-sensitive molecules such as nuclear factor 0B. 17 Recent studies indicate that TRX-1 is induced to protect host cells from various types of stresses, including ROS, viral infection, and ischemic insult. 17,18 Moreover, serum TRX-1 levels are recognized as an ORIGINAL ARTICLE 264 Pancreas & Volume 32, Number 3, April 2006 Received for publication October 4, 2005; accepted December 12, 2005. From the *Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, Kyoto, Japan; †Department of Experi- mental Therapeutics, Translational Research Center, Kyoto University Hospital, Kyoto, Japan; ‡Department of Biological Responses, Institute for Virus Research, Kyoto University, Kyoto, Japan and §Third Department of Internal Medicine, Kansai Medical University, Osaka, Japan This study was supported by grant-in-aid of the *Shimizu Foundation for the promotion of Immunology Research and grants-in-aid for †‡§Scientific Research (A15209024, A16790378, and C17590634) from the Japan Society for the Promotion of Science. Reprints: Akiyoshi Nishio, MD, PhD, Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, 54 Shogoin- Kawahara-cho, Sakyo-ku, Kyoto, 606-8507, Japan (e-mail: anishio@kuhp. kyoto-u.ac.jp). Copyr ight © Lippincott Williams & Wilkins. Unauthor iz ed reproduction of this article is prohibited.