The immune protective effect of the Mediterranean diet against chronic low-grade inflammatory diseases

Abstract

Dietary patterns high in refined starches, sugar, and saturated and trans-fatty acids, poor in natural antioxidants and fiber from fruits, vegetables, and whole grains, and poor in omega-3 fatty acids may cause an activation of the innate immune system, most likely by excessive production of proinflammatory cytokines associated with a reduced production of anti-inflammatory cytokines. The Mediterranean Diet (MedDiet) is a nutritional model inspired by the traditional dietary pattern of some of the countries of the Mediterranean basin. This dietary pattern is characterized by the abundant consumption of olive oil, high consumption of plant foods (fruits, vegetables, pulses, cereals, nuts and seeds); frequent and moderate intake of wine (mainly with meals); moderate consumption of fish, seafood, yogurt, cheese, poultry and eggs; and low consumption of red meat, processed meat products and seeds. Several epidemiological studies have evaluated the effects of a Mediterranean pattern as protective against several diseases associated with chronic low-grade inflammation such as cancer, diabetes, obesity, atherosclerosis, metabolic syndrome and cognition disorders. The adoption of this dietary pattern could counter the effects of several inflammatory markers, decreasing, for example, the secretion of circulating and cellular biomarkers involved in the atherosclerotic process. Thus, the aim of this review was to consider the current evidence about the effectiveness of the MedDiet in these chronic inflammatory diseases due to its antioxidant and anti-inflammatory properties, which may not only act on classical risk factors but also on inflammatory biomarkers such as adhesion molecules, cytokines or molecules related to the stability of atheromatic plaque.

Fig. (1)

Modulation of the Mediterranean diet on the immune factors providing protective effect against cardiovascular disease or cancer. Accumulation of oxidised low-density lipoprotein (oxLDL), starting in the fatty streaks, promotes the inflammatory response. Oxidized lipids and oxLDL trigger the expression of adhesion molecules (VCAM-1, mainly) and other mediators such as selectins and integrins, promoting the recruitment of monocytes into the subendothelial space in response to chemo-attractant cytokines. Successive accumulation of apoptotic cells, debris and cholesterol crystals form a necrotic core. Macrophages can be either classically activated (M1) or alternatively activated (M2). M1 monocytes display pro-inflammatory activity and could promote plaque vulnerability while, M2 monocytes are associated with homeostatic activity but could be pro-atherogenic in the early stages while promoting plaque stability in the later stages. Finally, in late stages atheromatic plaque may become unstable, leading to cap rupture, ensuing thrombosis and finally, cardiovascular events. The MedDiet exerts an anti-inflammatory and a modulating effect on CRP, interleukins such as IL-1, IL-6 as well as on TNF-α and its receptors, or chemoattractant molecules as MCP-1 or soluble adhesion molecules (sVCAM-1, sICAM-1, sE- and sP-Selectin). MedDiet triggers the alternative activation and exerts an immunomodulatory effect on biomarkers related to plaque stability such as IL-18, MMP-9 or TGF-β. It also can regulate the expression of leukocyte adhesion molecules including SLex, VLA-4 and LFA. IL-: interleukins; MMP-9: Metalloprotease-9; TNF-α: Tumor necrosis factor; TGF-β1: Transforming Growth Factor-β1; sVCAM-1: soluble vascular cell adhesion molecule; sICAM-1: Soluble intercellular adhesion molecule-1; sP-Selectin: Soluble platelet selectin; sE-Selectin: soluble endothelial selectin. Figure adapted [27, 28, 75, 76].