A well-functioning immune system is critical for survival. The immune system must be constantly alert, monitoring for signs of invasion or danger. Cells of the immune system must be able to distinguish self from non-self and furthermore discriminate between non-self molecules which are harmful (e.g., those from pathogens) and innocuous non-self molecules (e.g., from food). This Special Issue of Nutrients explores the relationship between diet and nutrients and immune function. In this preface, we outline the key functions of the immune system, and how it interacts with nutrients across the life course, highlighting the work included within this Special Issue. This includes the role of macronutrients, micronutrients, and the gut microbiome in mediating immunological effects. Nutritional modulation of the immune system has applications within the clinical setting, but can also have a role in healthy populations, acting to reduce or delay the onset of immune-mediated chronic diseases. Ongoing research in this field will ultimately lead to a better understanding of the role of diet and nutrients in immune function and will facilitate the use of bespoke nutrition to improve human health.

Background: Increasing intakes of long-chain n−3 polyunsaturated fatty acids (PUFAs) can decrease markers of immunity. However, dose- and age-related responses have not been identified. Objective: The objective was to determine the effects of different amounts of eicosapentaenoic acid (EPA) on innate immune outcomes in young and older males. Design: In a controlled, double-blind study, healthy young and older men consumed 1 of 4 supplements provided as capsules: placebo (corn oil) or different amounts of an oil providing 1.35, 2.7, or 4.05 g EPA/d for 12 wk. Blood samples were collected at baseline and after 12 wk. Results: EPA was incorporated in a linear dose-response fashion into plasma and mononuclear cell (MNC) phospholipids; incorporation was greater in the older men. EPA treatment did not alter neutrophil or monocyte phagocytosis, monocyte respiratory burst, or the production of inflammatory cytokines by MNCs in the young or older men. EPA treatment caused a dose-dependent decrease in neutrophil respiratory burst only in the older men. Increased incorporation of EPA into plasma or MNC phospholipids was associated with decreased production of prostaglandin E₂ by MNCs from both young and older men. Conclusions: Older subjects incorporate EPA into plasma and MNC phospholipids more readily than do younger subjects. Other than prostaglandin E₂ production, innate immune responses in young subjects are not affected by an EPA intake of ≤4.05 g/d. Older subjects are more sensitive to the immunologic effects of EPA, and the neutrophil respiratory burst is lower at higher EPA intakes.

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease of the joints and bones. Then-6 polyunsaturated fatty acid (PUFA) arachidonic acid (ARA) is the precursor of inflammatory eicosanoids which are involved in RA. Some therapies used in RA target ARA metabolism. Marinen-3 PUFAs (eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)) found in oily fish and fish oils decrease the ARA content of cells involved in immune responses and decrease the production of inflammatory eicosanoids from ARA. EPA gives rise to eicosanoid mediators that are less inflammatory than those produced from ARA and both EPA and DHA give rise to resolvins that are anti-inflammatory and inflammation resolving, although little is known about these latter mediators in RA. Marinen-3 PUFAs can affect other aspects of immunity and inflammation relevant to RA, including dendritic cell and T cell function and production of inflammatory cytokines and reactive oxygen species, although findings for these outcomes are not consistent. Fish oil has been shown to slow the development of arthritis in animal models and to reduce disease severity. A number of randomised controlled trials of marinen-3 PUFAs have been performed in patients with RA. A systematic review included 23 studies. Evidence is seen for a fairly consistent, but modest, benefit of marinen-3 PUFAs on joint swelling and pain, duration of morning stiffness, global assessments of pain and disease activity, and use of non-steroidal anti-inflammatory drugs.

The immune system acts to protect the host against pathogenic invaders. However, components of the immune system can become dysregulated such that their activities are directed against host tissues, so causing damage. Lymphocytes are involved in both the beneficial and detrimental effects of the immune system. Both the level of fat and the types of fatty acid present in the diet can affect lymphocyte functions. The fatty acid composition of lymphocytes, and other immune cells, is altered according to the fatty acid composition of the diet and this alters the capacity of those cells to produce eicosanoids, such as prostaglandin E2, which are involved in immunoregulation. A high fat diet can impair lymphocyte function. Cell culture and animal feeding studies indicate that oleic, linoleic, conjugated linoleic, gamma-linolenic, dihomo-gamma-linolenic, arachidonic, alpha-linolenic, eicosapentaenoic and docosahexaenoic acids can all influence lymphocyte proliferation, the production of cytokines by lymphocytes, and natural killer cell activity. High intakes of some of these fatty acids are necessary to induce these effects. Among these fatty acids the long chain n-3 fatty acids, especially eicosapentaenoic acid, appear to be the most potent when included in the human diet. Although not all studies agree, it appears that fish oil, which contains eicosapentaenoic acid, down regulates the T-helper 1-type response which is associated with chronic inflammatory disease. There is evidence for beneficial effects of fish oil in such diseases; this evidence is strongest for rheumatoid arthritis. Since n-3 fatty acids also antagonise the production of inflammatory eicosanoid mediators from arachidonic acid, there is potential for benefit in asthma and related diseases. Recent evidence indicates that fish oil may be of benefit in some asthmatics but not others.