Nutritional Modulation of Immune Function: Analysis of Evidence, Mechanisms, and Clinical Relevance

Abstract

It is well-established that the nutritional deficiency or inadequacy can impair immune functions. Growing evidence suggests that for certain nutrients increased intake above currently recommended levels may help optimize immune functions including improving defense function and thus resistance to infection, while maintaining tolerance. This review will examine the data representing the research on prominent intervention agents n-3 polyunsaturated fatty acids (PUFA), micronutrients (zinc, vitamins D and E), and functional foods including probiotics and tea components for their immunological effects, working mechanisms, and clinical relevance. Many of these nutritive and non-nutritive food components are related in their functions to maintain or improve immune function including inhibition of pro-inflammatory mediators, promotion of anti-inflammatory functions, modulation of cell-mediated immunity, alteration of antigen-presenting cell functions, and communication between the innate and adaptive immune systems. Both animal and human studies present promising findings suggesting a clinical benefit of vitamin D, n-3 PUFA, and green tea catechin EGCG in autoimmune and inflammatory disorders, and vitamin D, vitamin E, zinc, and probiotics in reduction of infection. However, many studies report divergent and discrepant results/conclusions due to various factors. Chief among them, and thus call for attention, includes more standardized trial designs, better characterized populations, greater consideration for the intervention doses used, and more meaningful outcome measurements chosen.

A Review of Micronutrients and the Immune System–Working in Harmony to Reduce the Risk of Infection

“…Vitamin A Downregulates IFNγ production [3,21] Vitamin D Calcitriol regulates antimicrobial protein expression (cathelicidin and defensin), which directly kill pathogens, especially bacteria [7, [39][40][41]; inhibits IFNγ production [27,[42][43][44][45] Table 1. Cont.…”

“…Iron Involved in regulation of cytokine production and action [3]; required for generation of pathogen-killing ROS by neutrophils during oxidative burst [7] Copper Accumulates at sites of inflammation [7,35]; part of copper/zinc-superoxide dismutase, a key enzyme in defense against ROS [8]; free-radical scavenger [58]; changes in copper homeostasis a crucial component of respiratory burst [8]; important for IL-2 production and response [7,35]; maintains intracellular antioxidant balance, suggesting important role in inflammatory response [8] Selenium Essential for function of selenoproteins that act as redox regulators and cellular antioxidants, potentially counteracting ROS produced during oxidative stress [2] Magnesium Can help to protect DNA against oxidative damage [37]; high concentrations reduce superoxide anion production [59] Differentiation, proliferation and normal functioning of T cells Vitamin A Involved in development and differentiation of Th1 and Th2 cells [60]; enhances TGF-β-dependent conversion of naïve T cells into regulatory T cells [8]; plays a role in acquisition of mucosal-homing properties by T and B cells [8] Vitamin D Homing of T cells to the skin [61]; calcitriol inhibits T-cell proliferation [7]; inhibitory effects mainly in adaptive immunity (e.g., Th1-cell activity) [7]; stimulatory effects in innate immunity [7]; inhibits the effector functions of T helper cells and cytotoxic T cells [27,62], but promotes the production of Tregs [27,62,63]; inhibitory effect on the differentiation and maturation of the antigen-presenting DCs, and helps program DCs for tolerance [27,[64][65][66] Vitamin C Roles in production, differentiation, and proliferation of T cells, particularly cytotoxic T cells [3,21] Vitamin E Enhances lymphocyte proliferation and T-cell-mediated functions [3]; optimizes and enhances Th1 response [3] Vitamin B6 Involved in lymphocyt...…”

“…Vitamin A Development and differentiation of Th 1 and Th2 cells [8]; maintains normal antibody-mediated Th2 response by suppressing IL-12, TNF-α, and IFN-γ production of Th1 cells [7] Vitamin D Calcitriol suppresses antibody production by B cells [7] Vitamin C Promotes proliferation of lymphocytes, resulting in increased generation of antibodies [21] Vitamin E Suppresses Th2 response [3] Vitamin B6 Required in endogenous synthesis and metabolism of amino acids, the building blocks of antibodies [7]; inhibits Th2 cytokine-mediated activity [8] Vitamin B12 Important for antibody production and metabolism, via folate mechanism [7, 8,35]; required for optimal clonal expansion [8] Folate Important for antibody production and metabolism [7,8,35] Zinc Involved in antibody production, particularly IgG [69,70] Selenium Helps to maintain antibody levels [35] Magnesium Cofactor in antibody synthesis, role in antibody-dependent cytolysis and IgM lymphocyte binding [38] Responses to antigen Vitamin A Normal functioning of B cells, necessary for generation of antibody responses to antigen [7]; required for B cell-mediated IgA antibody responses to bacterial polysaccharide antigens [8] Vitamin D Promotes antigen processing [8]; role in the down-regulation of MHC-II [35] Vitamin E Helps to form effective immune synapses between and Th cells [27]; increases proportion of antigen-experienced memory T cells [71] Folate Important for sufficient antibody response to antigens [35] Zinc Involved in antibody response [8]; important in maintaining immune tolerance (i.e., the ability to recognize "self" from "non-self") [27] Figure 2. Micronutrients have key roles at every stage of the immune response [2,[7][8][9].…”

“…It further enhances keratinocyte differentiation and lipid synthesis as well as fibroblast proliferation and migration [21]. Dietary or exogenous antioxidants such as vitamins C and E, in collaboration with endogenous antioxidant defenses, help to protect cell membranes from damage caused by free radicals generated during normal metabolism, as well as through exposure to toxins and pollutants [7,8,27]. Although reactive oxygen species (ROS) are essential for cell communication [77], for example, at high concentrations they can denature structural and functional cell components such as lipids and proteins [78,79].…”

Pharmacological plasticity—How do you hit a moving target?

“…In the meantime, it has been well established that changing the type of dietary fatty acid can have marked effects on the structural type of eicosanoid generated. For example, increasing dietary intake of omega‐3 fatty acids, which occur in high quantities in fish, reduces the amounts and conversion of the n‐6 fatty acid arachidonic acid to metabolites such as PGE2 and leads to synthesis of metabolites that either have different or limited biological activities, as well as exerting inhibitory effects pe se on inflammatory mediator production . Moreover, omega‐3 fatty acids modify the composition of the gut microbiome, promoting bacteria with a less proinflammatory profile .…”