Inflammation and Chronic Disease
Numerous chronic diseases are associated with inflammation, including cardiometabolic disorders such as heart disease, obesity, and diabetes; autoimmune disorders such as rheumatoid arthritis and multiple sclerosis; gastrointestinal disorders such as inflammatory bowel disease; and neurodegenerative disorders such as Parkinson’s. While acute inflammation is a normal, helpful response to infection or trauma; chronic, unregulated inflammation self-perpetuates and continues to drive the destructive cycle of inflammation and disease. Physical injury, emotional stress, allergies, infections, environmental toxicants, and gut dysbiosis can all propagate inflammation. Both the innate and adaptive immune systems are involved in mediating chronic inflammatory processes, with additional imbalances between cell-mediated and humoral immune responses.
Cyclical Role of Inflammation in Metabolic Syndrome
Metabolic Syndrome involves risk factors such as central obesity, dyslipidemia, and glucose dysregulation, and is thus a great model for studying inflammation. In obesity, as adipose tissue expands, adipokines release macrophage-chemoattractant protein-1 which recruits phagocytic macrophages, a vital part of innate immunity, to infiltrate adipose tissue. Macrophages, which view adipose tissue as foreign, utilize ROS and initiate adaptive defenses by calling upon T and B cells to damage the already-inflamed tissue. This leads to the secretion of pro-inflammatory cytokines such as IL-6 and tumor necrosis factor alpha. IL-6 promotes the release of pro-inflammatory C-reactive protein from the liver. Increased adipose tissue also leads to higher levels of leptin, a satiety hormone. Despite higher levels of leptin, obese individuals develop decreased sensitivity to leptin, thereby promoting more inflammation and ectopic fat storage. The increased cytokine and NFκB production leads to oxidative stress, which in turn disrupts proper mitochondrial regulation, lipid metabolism, and insulin functioning; thus, contributing to insulin resistance.
So, not only can obesity contribute to inflammation—but inflammation can also induce obesity as a result of driving leptin and insulin resistance. Moreover, increased dietary fat intake promotes gut dysbiosis due to a reduction in levels of beneficial gut bacteria and growth in harmful bacteria. This contributes to endotoxemia as a result of gut bacteria-derived lipopolysaccharides production, which further activates pro-inflammatory cytokines and hinders insulin secretion. Since environmental toxicants and ‘endocrine disruptors’ such as persistent organic pollutants accumulate in adipose tissue, this continues to exacerbate inflammatory cytokine and NFκB production, leading to altered lipid and glucose metabolism and contributing to endocrine and CVD. In the arterial intima, oxidation of LDL begins the inflammatory process of atherogenesis. Plaque formation starts due to a lesion in the endothelial layer, causing LDL to be transported from the blood into the intima. Here, the LDL becomes oxidized by free radicals, which results in the release of monocytes into the intima. Monocytes differentiate into macrophages, which then ingest the oxidized LDL particles and become foam cells. This leads to secretion of T-cells from blood and SMCs from the media, proliferating the cytokine-mediated inflammatory response.
Inflammation in Autoimmunity
Multiple sclerosis is also associated with inflammation. According to the hygiene hypothesis, infants with reduced exposure to antigens in their first year do not properly develop oral tolerance as a result of inadequate inoculation by antigens for their immune systems to become fully competent. Immune competence is the balance of Th1 (cell mediated) and Th2 (humoral) immune responses. Impaired immune defenses can result in chronic infections and inflammation, creating an environment for increased molecular mimicry and subsequent autoimmunity. Autoimmunity is generally associated with increased Th1 cytokine expression such as INF-γ and IL-2, and reduced Th2 cytokines such as IL-10. In MS, T-reg cells, which are important in preventing activation of auto-reactive T-cells, are reduced.
Increases in Th1 lymphocytes which circulate systemically, lead to increased inflammatory cytokines, reactive oxygen species, and matrix metallo-proteinases in the brain, worsening blood–brain barrier permeability and contributing to brain lesion formation. Moreover, MS risk factors such as vitamin D deficiency, increased intestinal permeability, food hypersensitivities, and stress, can all contribute to inflammatory processes.
Dietary and Lifestyle Approaches to Reduce Inflammation
Obesity and CVD benefit from anti-inflammatory, high fiber and low-glycemic diets such as the Mediterranean diet (MD). The MD is abundant in phytonutrient and antioxidant-rich fruits, vegetables, whole grains and legumes; low in refined sugars; and has a high ratio of omega-3 to omega-6 fatty acids. Omega-3 fatty acids increase anti-inflammatory eicosanoid production. The MD limits sources of trans and saturated fats such as processed foods and red meat and instead encourages consumption of mono- and polyunsaturated sources of fat such as oily fish (salmon), olive oil, and nuts (walnuts) and seeds (flaxseeds). The MD is high in carotenoids, flavonoids, magnesium, selenium, and vitamins C, and E—while garlic and onions contribute to inhibiting inflammatory cyclooxygenase 2 and lipoxygenase enzymes.
Vitamin D supplementation can increase IL-10 and T-reg cells, which can balance the Th1/Th2 systems. Strain-specific probiotics such as Bifidobacterium bifidum can also decrease gut dysbiosis and inflammation. Since autoimmune disease patients often have concomitant autoimmune disorders such as Celiac disease or increased intestinal permeability and food hypersensitivities, avoidance of gluten and other food allergens can also help. A trial of an elimination diet and life-long adherence to a gluten-free diet may substantially improve symptoms due to reducing inflammation systemically. Since dietary antigens (gluten, dairy, eggs, etc.) can trigger imbalances in Th1 and Th2 cytokines, in chronic autoimmune mediated inflammation, eliminating the trigger is the best option.
