MODIFICATION OF INFLAMMATORY ASPECTS OF IMMUNE FUNCTION BY NUTRIENTS

The pro-inflammatory cytokines interleukin 1 (IL1) interleukin 6 (IL6) and tumour necrosis factor-alpha (TNF), and reactive oxygen species ( ROS), play a-major role in inflammatory aspects of immune function. Th ey are closely linked with pathology in a wide range of diseases and c ondition which have an inflammatory basis. Alterations in the intake o f fats, antioxidant nutrients, protein and specific amino acids change many aspects of inflammation by interacting with cytokine and ROS bio logy, thereby providing a means of modulating inflammation. Mortality and morbidity, in a diverse range of diseases, have been linked with e xcessive or untimely oxidant and pro-inflammatory cytokine production. Evidence of oxidative damage has been observed in sepsis, HIV and hep atitis infection, cancer, diabetes mellitus, alcoholic liver disease a nd cystic fibrosis. ROS produced during the inflammatory response enha nces pro-inflammatory cytokine production by activation of nuclear fac tor kappa B (NF kappa B). The interaction is an important part of the up-regulation of inflammatory aspects of immune function. The interact ion between ROS and cytokines has the potential to damage the host but is held in check by the antioxidant defences. Nutrient intake directl y and indirectly influences antioxidant defence. Glutathione is a majo r endogenous antioxidant and is important for lymphocyte replication. Vitamin B, and riboflavin participate in the maintenance of glutathion e status. Vitamin B, acts as a cofactor in the synthesis of cysteine ( the rate limiting precursor for glutathione biosynthesis) and riboflav in is a cofactor for glutathione reductase. Deficiencies in vitamins E , B, and riboflavin reduce cell numbers in lymphoid tissues of experim ental animals and produce functional abnormalities in the cell mediate d immune response. Sulphur amino acid deficient rats exhibit an impair ed ability to synthesise glutathione during inflammation and have incr eased numbers of neutrophils in lung. Ascorbic acid and tocopherols ex ert anti-inflammatory effects in studies in man and animals. In humans , dietary supplementation with ascorbic-acid, tocopherols and vitamin B, enhances a number of aspects of lymphocyte function-In smokers indi ces of inflammation inversely relate to the intakes of vitamins C and E. Studies in healthy subjects, patients and experimental animals clea rly demonstrate that unsaturated fats modulate pro-inflammatory cytoki ne biology. In general n-6 polyunsaturated fatty acids enhance, and n- 3 PUFAs and monounsaturated fatty acids suppress, cytokine mediated as pects of inflammation. In addition, n-6 PUFAs and cholesterol enhance and n-3 PUFAs suppress cytokine production. Fats rich in n-3 PUFAs are efficacious in a number of inflammatory diseases, however in smokers indices of inflammation are enhanced in subjects consuming greater tha n 5% of dietary energy in the form of n-6 PUFAs. Fats may modulate cyt okine biology by a number of mechanisms closely linked to membrane pho spholipid composition. As a consequence of diet induced change, altera tions in prostaglandin, leukotriene and diacyl glycerol production, pr otein kinase C activation and fluidity may occur. Recent studies sugge st that changes in bulk membrane fluidity are unlikely to underlie the substantial modulatory effects of fats on cytokine biology. In conclu sion nutrients have a major potential for modulating inflammatory aspe cts of immune function due to interaction with three main areas whereb y inflammation is prosecuted and controlled. Firstly by changing provi sion of substrate for the synthesis of molecules for components for th e executive and control systems (protein, sulphur amino acids, glutami ne). Secondly by modulating the composition of the membranes of cells involved in the inflammatory process (unsaturated fatty acids and chol esterol) and thirdly by influencing the interaction between ROS and NF kappa B activation (sulphur amino acids, vitamins C and E, and ribofl avin). (C) 1998 Elsevier Science Inc.