Current Pharmaceutical Design, 2009, 15, 000-000 1 1381-6128/09 $55.00+.00 © 2009 Bentham Science Publishers Ltd. -3 Polyunsaturated Fatty Acids and Immune-Mediated Diseases: Inflammatory Bowel Disease and Rheumatoid Arthritis C. Ruggiero* 1 , F. Lattanzio 2 , F. Lauretani 3 , B. Gasperini 1 , C. Andres-Lacueva 4 and A. Cherubini 1 1 Institute of Gerontology and Geriatrics, Department of Clinical and Experimental Medicine, University of Perugia, Perugia, Italy; 2 Scientific Director, Istituto Nazionale di Ricovero e Cura dell’Anziano INRCA), Ancona, Italy. 3 Geriatric Unit, Geriatric-Rehabilitation Department, University Hospital of Parma, Parma, Italy; 3 Nutrition and Food Science Department-XaRTA INSA, Pharmacy School, University of Barcelona, Barcelona, Spain Abstract: Inflammation is part of the normal host response to infection and injury. However, inappropriate inflammation contributes to several diseases, including inflammatory bowel disease (IBD) and rheumatoid arthritis (RA). Both conditions are characterized by the excessive production of inflammatory cytokines, arachidonic acid (AA)-derived eicosanoids, and other inflammatory agents (e.g., reactive oxygen species, adhesion molecules). By virtue of their anti- inflammatory action, -3 polyunsaturated fatty acids (PUFA) may be beneficial in inflammatory diseases. A large body of evidence supports a protective effect of -3 PUFA in experimental animal and ex-vivo models of Crohn’s disease (CD), Ulcerative colitis (UC) and Rheumatoid arthritis (RA). Although fish oil supplementation in patients with IBD results in -3 PUFA incorporation into gut mucosal tissue and modification of inflammatory mediator profiles, the evidence of clinical benefits of -3 PUFA is weak. On the other hand, more convincing data support the efficacy of -3 PUFA in reducing pain, number of tender joints, duration of morning stiffness, use of non-steroidal anti-inflammatory drugs and improving physical performance in RA patients. In both IBD and RA further clinical trials with large sample size are needed to clarify the efficacy of -3 PUFA as a treatment. Keywords: Polyunsaturated fatty acids, inflammation, reumathoid arthritis, inflammatory bowel disease, Crohn disease, Ulcerative colitis. 1. INTRODUCTION Chronic autoimmune diseases, such as inflammatory bowel diseases (IBD) and rheumatoid arthrirtis (RA), are inflammatory-mediated conditions characterized by an uncontrolled inflammatory response causing an excessive damage to the host tissues and resulting in a disease status. Autoimmune diseases affect up to 5-8% of the United States population and are among the most important conditions causing disability and death in Western societies [1, 2]. A common characteristic of IBD and RA is the excessive production of inflammatory mediators, including eicosanoids and cytokines, that are destructive for body’s tissues. Eico- sanoids are the most important mediators and regulators of the immune responses. They represent the key link between dietary PUFA and autoimmune diseases because they are directly generated from -6 or -3 PUFA phospholipids of the immune cell membranes whose composition reflects PUFA dietary intake [3]. Both the increasing prevalence of autoimmune diseases and the switch from -3 to -6 PUFA dietary intake obser- ved in Western countries during the past decades support the hypothesis that PUFA may be an explanatory and modifiable environmental factor in the pathogenesis of autoimmune diseases. Indeed, high -6 compared to -3 PUFA dietary *Address correspondence to this author at the Department of Clinical and Experimental Medicine, Institute of Gerontology and Geriatrics, Ospedale S. Maria della Misericordia, P.le Menghini, 1 06123, Perugia, Italy; Tel: +39-075-578-3722; Fax: +39-075-5783878; E-mail: ???????????? intake may increase the amount of -6 PUFA membrane phospholipids of immune cells and, therefore, protract the inflammatory processes predisposing to or exacerbating inflammatory diseases [4]. A large number of preclinical and clinical studies have been performed on the relationship between PUFA, inflam- matory biomarkers and clinical outcomes of patients with autoimmune-mediated disorders [4]. Although a clear asso- ciation between the shifted balance of -6 and -3 PUFA intake and the risk of autoimmune diseases is lacking, many investigators recognised the potential of -3 PUFA in dampening excessive inflammatory responses in most inflammatory chronic diseases and conditions [3]. This review summarizes the preclinical and clinical scientific evidence concerning the effects of PUFA, either from diet or supplements, on inflammatory biomarkers, clini- cal symptoms and clinical outcomes of patients with IBD and RA. 2. SELECTION CRITERIA The studies included in this review were collected by means of a systematic Medline search from 1966 to July 2009, using the following keywords: (IBD OR Crohn’s disease OR Ulcerative colitis) AND (-3 OR polyunsa- turated fatty acids OR PUFA OR DHA OR EPA OR fish oil), as well as (Rheumatoid arthritis) AND (-3 OR poly- unsaturated fatty acids OR PUFA OR DHA OR EPA OR fish oil). Reference lists from identified articles were also scrutinized for pertinent studies that had not been indexed in