U NCORR E CTED P ROOF Brain, Behavior, and Immunity xxx (2006) xxx–xxx www.elsevier.com/locate/ybrbi 0889-1591/$ - see front matter  2006 Published by Elsevier Inc. doi:10.1016/j.bbi.2006.02.001 YBRBI 972 No. of Pages 7; Model 5+ ARTICLE IN PRESS 2 March 2006 Disk Used Sasikala (CE) / Vijayakumar (TE) Ibuprofen use, endotoxemia, inXammation, and plasma cytokines during ultramarathon competition David C. Nieman a,b,¤ , Dru A. Henson a,b , Charles L. Dumke a,b , Kevin Oley a,b , Steven R. McAnulty a,b , J. Mark Davis c , E. Angela Murphy c , Allan C. Utter a,b , Robert H. Lind a,b , Lisa S. McAnulty a,b , Jason D. Morrow d a Department of Health, Leisure, and Exercise Science, Fischer Hamilton/Nycom Biochemistry Laboratory, Appalachian State University, Boone, NC 28608, USA b Department of Biology, Fischer Hamilton/Nycom Biochemistry Laboratory, Appalachian State University, Boone, NC 28608, USA c Department of Exercise Science, University of South Carolina, Columbia, SC 29208, USA d Department of Medicine and Pharmacology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA Received 20 January 2006; received in revised form 5 February 2006; accepted 6 February 2006 Abstract The primary purpose of this study was to measure the inXuence of ibuprofen use during the 160-km Western States Endurance Run on endotoxemia, inXammation, and plasma cytokines. Subjects included 29 ultramarathoners who consumed 600 and 1200 mg ibuprofen the day before and on race day, respectively, and 25 controls that competed in the race but avoided ibuprofen and all other medications. Blood and urine samples were collected the morning prior to and immediately following the race, and subjects recorded muscle soreness during the week following the race using a 10-point Likert scale (DOMS). Race time (25.8 § .6 and 25.6 § .8 h, respectively) and ratings of perceived exertion (RPE, 6–20 scale) (14.6 § .4 and 14.5 § .2, respectively) did not diVer signiWcantly between ibuprofen users and nonus- ers. Ibuprofen use compared to nonuse was linked to a smaller increase in urine creatinine (P D .038), higher plasma levels of lipopolysac- charide (group eVect, P D .042), and greater increases (pre-to-post race) in serum C-reactive protein and plasma cytokine levels for interleukin (IL)-6, IL-10, IL-8, IL-1ra, granulocyte colony-stimulating factor, monocyte chemotactic protein 1, and macrophage inXam- matory protein 1 beta, but not tumor necrosis factor alpha. Post-race DOMS and serum creatine kinase levels did not diVer signiWcantly between ibuprofen users and nonusers (20,621 § 3565 and 13,886 § 3068 cal/L, respectively, P D .163). In conclusion, ibuprofen use com- pared to nonuse by athletes competing in a 160-km race did not alter muscle damage or soreness, and was related to elevated indicators of endotoxemia and inXammation.  2006 Published by Elsevier Inc. Keywords: Immunity; Running; Lipopolysaccharide; InXammation; Gastrointestinal 1. Introduction Athletes competing in marathons and ultramarathons experience large increases in plasma cytokine levels including interleukin (IL)-6, IL-10, IL-1ra, IL-8, granulo- cyte colony-stimulating factor or G-CSF, monocyte chemotactic protein 1 or MCP-1, and macrophage inXam- matory protein 1 beta or MIP-1) (Nieman et al., 2001, 2002, 2003, 2005; Ostrowski et al., 2000; Suzuki et al., 2000, 2002). Exercise-induced increases in these cytokines vary substantially between athletes (Nieman et al., 2001, 2005). Potential triggers of cytokine release during exer- cise include leakage of endotoxins (lipopolysaccharide or LPS) from the intestines during exercise, elevation in cat- echolamines and cortisol, high core body temperature, * Corresponding author. Fax: +1 828 262 3138. E-mail address: niemandc@appstate.edu (D.C. Nieman). 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43