Dietary fatty acid modulation of mucosally-induced tolerogenic immune responses

Abstract

Immunological unresponsiveness or hyporesponsiveness (tolerance) can be induced by feeding protein antigens to naïve animals. Using a classical oral ovalbumin gut-induced tolerance protocol in BALB/c mice we investigated the effects of dietary n-6 and n-3 polyunsaturated fatty acids (PUFA) on high-and low-dose oral tolerance (and in non-tolerised animals, i.e. effects of antigen challenge alone) in relation to lymphoproliferative, cytokine and antibody responses. Fish oil rich in long-chain n-3 fatty acids decreased both T-helper (Th) 1- and Th2-like responses. In contrast, borage (Borago officinalis) oil rich in n-6 PUFA, of which γ-linolenic acid is rapidly metabolised to longer-chain n-6 PUFA, increased Th1-like responses and decreased Th2-like responses, and possibly enhanced suppressor cell or Th3-like activity. These findings are in general agreement with other studies on the effects of long chain n-3 PUFA on immune system functions, and characterise important differences between long-chain n-3 and n-6 PUFA, defining more precisely and broadly the immunological regulatory mechanisms involved. They are also discussed in relation to autoimmune disease.

Hempseed as a nutritional resource: An overview

“…A recent clinical study with topically applied hempseed oil has already demonstrated its usefulness in healing mucosal skin wounds after eye, nose and throat surgery (Grigoriev, 2002). This finding is in line with numerous other clinical studies that have demonstrated the utility of EFAs and other PUFAs in healing and immune response (Manku et al, 1982(Manku et al, , 1984Bordoni et al, 1988;Oliwiecki et al, 1991;Sakai et al, 1994;Yu & Björkstén, 1998;Derek & Meckling-Gill, 1999;Harbige et al, 2000;Harbige & Fisher, 2001;Horrobin, 2000;Simopoulos, 2002a,b). The fatty acid profile of hempseed oil is remarkably similar to that of black currant seed oil, which also seems to have a beneficial impact on immunologic vigor (Wu et al, 1999;Barre, 2001).…”

Lyprinol™ only partially improves indicators of small intestinal integrity in a rat model of 5-fluorouracil-induced mucositis

“…The main inflammatory mediators produced by these pathways are eicosanoids, PGE 2 and LTB 4 . 30,31 The COX-1 pathway is involved in gut, kidney and blood function and thus its inhibition is undesirable. 32 The high n-3 PUFA content of Lyprinol™ and fish oil may account for their anti-inflammatory properties in the current study.…”

Fatty acids, the immune response, and autoimmunity: A question of n−6 essentiality and the balance between n−6 and n−3

“…It is possible therefore that AA accretion, in addition to growth requirements, is linked to thymic programming (education) in relation to autoreactive T cells and tolerogenic mechanisms and the subsequent development of autoimmune and allergic disorders (11,79). In summary, there is therefore much evidence for an essential role for n-6 fatty acids and their oxygenated metabolites in the lymphoid system but not for n-3 fatty acids.…”

“…The Th cytokine pattern also depends on the dose and properties of antigens, site of exposure, and the environment in which the T cells are found, e.g., production of antigen-presenting cellderived IL-12 can direct Th1 responses via induction of IFN-γ (4,6-8). The dietary fatty acid effect on the nutritional microenvironment of the cell should now also be included with the foregoing factors that influence Th cells and their cytokine pattern (9)(10)(11).…”