Digestive Diseases and Sciences, Vol. 50, No. 8 (August 2005), pp. 1444–1453 ( C  2005) DOI: 10.1007/s10620-005-2859-3 Effect of Bacterial Chemotactic Peptides on Intestinal Inflammation in Animal Models of Acute and Chronic “Relapsed” Colitis GERARDO A. HERN ´ ANDEZ, PhD, MELANIE R. VALENT ´ IN, BS, and CAROLINE B. APPLEYARD, PhD It is known that bacterial chemotactic peptides such as formyl-methionyl-leucyl-phenylalanine (fMLP) exacerbate colitis during the acute phase, but the precise role of fMLP during chronic “relapse” is unknown. In this study we examined the effect of bacterial peptides in animal models of acute and chronic “relapsed” colitis. Different parameters were evaluated, such as tissue damage, myeloperoxidase activity, and mucosal function. In acute trinitrobenezene sulfonic acid colitis, fMLP had significant adverse effects on mucosal function and worsened several parameters. In contrast, in chronic “relapsed” colitis the ability of fMLP to exacerbate the inflammation was dependent on whether it was confined to the lumen of the colon. Bacterial peptides such as fMLP appear to play a different role in the acute phase of inflammation compared with the chronic phase, depending on the integrity of the mucosal barrier. KEY WORDS: rat; colitis; trinitrobenzenesulfonic acid; inflammatory bowel disease; bacterial peptides. Ailments of the gastrointestinal tract such as ulcerative colitis and Crohn’s disease—collectively termed inflam- matory bowel disease (IBD)—can be very debilitating. Although many therapies are currently available, there is still no cure for this disease, whose main symptoms in- clude abdominal pain, diarrhea, weight loss, fever, and bleeding in Crohn’s disease (1). One of the major rea- sons that the pathophysiological basis of this disease re- mains unclear is the apparent multifactorial nature of IBD, with its suggested interactions among the immune system, the environment, and genetic susceptibility. Although the Manuscript received September 23, 2004; accepted November 3, 2004. From the Department of Physiology, Ponce School of Medicine, Ponce, Puerto Rico 00732-7004. The experiments reported herein were performed in accordance with the principles described in the “Guide for the Care and Use of Laboratory Animals,” Publication No. DHHS (NIH) 86-23. This work was supported by National Institutes of Health grants including National Research Service Award F31DK60245 from the NIDDK (G.A.H.), S06-GM08239 (C.B.A.), and G12-RR03050 (C.B.A.). Address for reprint requests: Caroline B. Appleyard, PhD, Department of Physiology, Ponce School of Medicine, P.O. Box 7004, Ponce, Puerto Rico 00732-7004; cappleyard@psm.edu. causes of IBD are not yet known, an etiologic pathway has been proposed that would involve the presence of an initiating factor or antigen that gains access to the subep- ithelial space. These events may be facilitated or amplified by undefined abnormalities of the gastrointestinal tract and/or some kind of genetically determined vulnerability to external agents. The antigen-driven response may be ei- ther an appropriate one directed against an unrecognized pathogen or an inappropriate, overly aggressive reaction to the resident luminal flora (2). A great deal of interest has centered on the possibil- ity of the role of a specific pathogen since the discov- ery of Helicobacter pylori as the main causative factor in active chronic gastritis (3). During the last decade, re- markable efforts have been undertaken to find the link between bacteria and IBD, yet a specific pathogen has not been identified. Swidsinski et al., using very sophisticated techniques such as quantitative polymerase chain reaction with subsequent cloning and sequencing, fluorescence in situ hybridization, and electron microscopy, were unable to identify any specific pathogens in the mucosal flora of patients with IBD (4). Despite this lack of direct evidence 1444 Digestive Diseases and Sciences, Vol. 50, No. 8 (August 2005) 0163-2116/05/0800-1444/0 C  2005 Springer Science+Business Media, Inc.