Send Orders for Reprints to reprints@benthamscience.ae Endocrine, Metabolic & Immune Disorders - Drug Targets, 2015, 15, 000-000 1 1871-5303/15 $58.00+.00 © 2015 Bentham Science Publishers Mediterranean Diet and Low-grade Subclinical Inflammation: The Moli-sani Study Marialaura Bonaccio * , Chiara Cerletti, Licia Iacoviello and Giovanni de Gaetano Department of Epidemiology and Prevention, IRCCS Istituto Neurologico Mediterraneo NEUROMED, Pozzilli (IS), Italy Abstract: Low-grade chronic inflammation is an underlying pathophysiological mechanism linking risk factors and/or metabolic disorders to increased risk of chronic degenerative disease. A meat-based pattern, as the Western type diet, is positively linked to higher levels of some important biomarkers of inflammation, such as C-reactive protein (CRP), interleukin-6 and fibrinogen. Conversely, a Mediterranean-like eating behavior is associated with lower degree of these biomarkers thus suggesting an anti-inflammatory action of its main food components. This chapter goes through the most important investigations addressing the relationship between dietary habits and subclinical inflammation. Attention was focussed on the findings from the Moli-sani study: this is a large prospective cohort study that recruited 24,325 men and women from the general population of the Molise Region, a Southern Italian area, with the aim of investigating genetic and environmental risk/protection factors for cardiovascular and tumor disease. For the first time, the Moli-sani study carefully investigated the Mediterranean diet as an environmental determinant of both platelet and white blood cell counts, starting from the hypothesis that a diet rich in healthy compounds could favorably influence the production and/or the clearance of these two cellular biomarkers of low-grade inflammation. Additionally, evidence from this large Italian cohort showed that a Mediterranean-like diet was closely associated with relatively lower values of glucose, lipids, CRP, blood pressure and 10-year cardiovascular risk, while the consumption of healthy foods with high rather than low content in antioxidant vitamins and phytochemicals was associated with lower blood pressure and CRP plasma levels at least in men. Keywords: Antioxidants, biomarkers of inflammation, cardiovascular disease, cancer, low-grade inflammation, mediterranean diet. BIOMARKERS OF CHRONIC LOW-GRADE INFLAMMATION Low-grade inflammation is a condition not yet uniformely defined: several biomarkers and different levels of their increase have been reported to be associated with a condition of low-grade inflammation [1]. Here a low-grade inflammation is intended as a subclinical condition (systemic or local, often chronic) characterized by increased levels of plasmatic and/or cellular biomarkers of inflammation (e.g. C-reactive protein, platelet or leukocyte counts) without any apparent clinical sign. In the absence of an acute inflammatory condition (e.g. CRP <10 mg/L or WBC <=10 x10 9 /L), a low-grade inflammation may reflect different degrees of variance within the normal range of each specific biomarker. A low-grade inflammation has also been defined as an underlying pathophysiological mechanism linking risk factors or metabolic disorders (as oxidative stress, obesity, diabetes, dyslipidemia, etc.) to an increased risk of chronic degenerative disease [1]. C-reactive protein is the best- studied marker of subclinical inflammation [2] but several other inflammatory biomarkers have been associated with *Address correspondence to this author at the Department of Epidemiology and Prevention, IRCCS Istituto Neurologico Mediterraneo NEUROMED, Pozzilli (IS), Italy, Via dell'Elettronica, 86077 POZZILLI (IS), Italy; Tel: +39.0865.929.653; Fax: +39.0865.927.575; E-mail: marialaura.bonaccio@moli-sani.org low-grade inflammation. Increased levels of interleukins, fibrinogen and the adhesion molecules E-selectin, intercellular adhesion molecule-1 (ICAM-1), and vascular adhesion protein-1 (VCAM-1), have been shown to be directly associated and to predict type-2 diabetes, cardiovascular disease and cancer; conversely, levels of anti-inflammatory biomarkers, such as adiponectin, have been associated with the reduction of cardiovascular disease, type-2 diabetes, and obesity-related cancer [1]. A fatty meal may represent an acute in vivo challenge that induces a low-grade inflammatory reaction. In a group of subjects at different degree of cardiovascular risk, the post-prandial condition, characterized by acutely elevated levels of triglyceride-rich lipoproteins, was accompanied by significant changes in haematological parameters: increased white blood cell counts, in particular granulocytes, increased platelet count and decreased mean platelet volume [3, 4]. The changes were statistically significant, although in a small range of differences, and were accompanied by the cell surface expression of activation markers and myeloperoxidase degranulation within granulocytes. The post-prandial state, a physiological phenomenon that may occur several times a day, could lead to a complex series of events (including endotoxemia) that may initiate and develop atherothrombosis. The occurrence of similar predictive biomarkers in conditions and diseases being apparently different for their pathogenesis, such as vascular diseases and cancer, together