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. They are closely linked with pathology in a wide range of diseases and condition which have an inflammatory basis. Alterations in the intake of fats, antioxidant nutrients, protein and specific amino acids change many aspects of inflammation by interacting with cytokine and ROS biology, thereby providing a means of modulating inflammation. Mortality and morbidity, in a diverse range of diseases, have been linked with excessive or untimely oxidant and pro-inflammatory cytokine production. Evidence of oxidative damage has been observed in sepsis, HIV and hepatitis infection, cancer, diabetes mellitus, alcoholic liver disease and cystic fibrosis. ROS produced during the inflammatory response enhances pro-inflammatory cytokine production by activation of nuclear factor kappa B (NF kappa B). The interaction is an important part of the up-regulation of inflammatory aspects of immune function. The interaction between ROS and cytokines has the potential to damage the host but is held in check by the antioxidant defences. Nutrient intake directly and indirectly influences antioxidant defence. Glutathione is a major endogenous antioxidant and is important for lymphocyte replication. Vitamin B and riboflavin participate in the maintenance of glutathione status. Vitamin B acts as a cofactor in the synthesis of cysteine (the rate limiting precursor for glutathione biosynthesis) and riboflavin is a cofactor for glutathione reductase. Deficiencies in vitamins E, B, and riboflavin reduce cell numbers in lymphoid tissues of experimental animals and produce functional abnormalities in the cell mediated immune response. Sulphur amino acid deficient rats exhibit an impaired ability to synthesise glutathione during inflammation and have increased numbers of neutrophils in lung. Ascorbic acid and tocopherols exert 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 indices of inflammation inversely relate to the intakes of vitamins C and E. Studies in healthy subjects, patients and experimental animals clearly demonstrate that unsaturated fats modulate pro-inflammatory cytokine biology. In general n-6 polyunsaturated fatty acids enhance, and n-3 PUFAs and monounsaturated fatty acids suppress, cytokine mediated aspects 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 than 5% of dietary energy in the form of n-6 PUFAs. Fats may modulate cytokine biology by a number of mechanisms closely linked to membrane phospholipid composition. As a consequence of diet induced change, alterations in prostaglandin, leukotriene and diacyl glycerol production, protein kinase C activation and fluidity may occur. Recent studies suggest that changes in bulk membrane fluidity are unlikely to underlie the substantial modulatory effects of fats on cytokine biology. In conclusion nutrients have a major potential for modulating inflammatory aspects of immune function due to interaction with three main areas whereby inflammation is prosecuted and controlled. Firstly by changing provision of substrate for the synthesis of molecules for components for the executive and control systems (protein, sulphur amino acids, glutamine). Secondly by modulating the composition of the membranes of cells involved in the inflammatory process (unsaturated fatty acids and cholesterol) and thirdly by influencing the interaction between ROS and NF kappa B activation (sulphur amino acids, vitamins C and E, and riboflavin). (C) 1998 Elsevier Science Inc.
