Interleukins 1 and 6 and tumour necrosis factor orchestrate a co-ordinated series of metabolic changes following invasions by pathogens. The changes are designed to destroy the pathogen. The response is characterized by fever, proteolysis in peripheral tissues, acute phase protein and antioxidant synthesis, and enhancement of the activity of the immune system. Cytokine production is enhanced by free radicals. Damage to the host may occur as a consequence. The deterious actions of these molecules are held in check by sophisticated antioxidant defences and systems which exert feedback control on cytokine biology. Nutrients have a profound effect upon the production and actions of cytokines. Protein energy malnutrition, dietary n-3 polyunsaturated fatty acids and vitamin E suppress cytokine production and actions. An opposite influence is exerted by n-6 polyunsaturated fatty acids, poor antioxidant defence, and supplementation of the diet with protein and branched chain amino acids. The synthesis of acute phase proteins and glutathione is dependent upon the adequacy of dietary sulphur amino acid intake. The consequences of the modulatory effects of previous and concurrent nutrient intake on cytokine biology are depletion of resources and damage to the host, which ranges from mild and temporary to severe, chronic or lethal.

Amino Acids↗

PubMedDate not supplied

Nutritional modulation of cytokine biology.

The pro-inflammatory cytokines and oxidant molecules produced during the inflammatory response, which follows infection and injury, may be beneficial, or detrimental to the patient, depending on the amounts and contexts in which they are produced. Aberrant or excessive production has been implicated in inflammatory disease, and sepsis. The upregulation of cytokine production by NF kappa B and NFIL-6 activation by oxidants increases the likelihood of cytokine-induced mortality and morbidity. Complex systems exist for the control of cytokine production and oxidant actions. The former include the hormones of the hypothalamo-pituitary-adrenal axis, acute phase proteins, and endogenous inhibitors of interleukin (IL)-1 and tumor necrosis factor (TNF). The latter include endogenously synthesized antioxidants, such as glutathione and dietary antioxidants, such as tocopherols, ascorbates and cachectins. Nutrients change cytokine production and potency by influencing tissue concentrations of many of the molecules involved in cytokine biology. Monounsaturated fatty acids and omega-3 polyunsaturated fatty acids (PUFAs) suppress TNF and IL-1 production and actions, while n-6 PUFAs exert the opposite effect. Changes in eicosanoid production are more likely to underlie this effect than alterations in membrane fluidity. Low antioxidant intake results in enhanced cytokine production and effects. The anorexia that follows infection and injury, may be purposeful to permit release of substrate from endogenous sources to support and control the inflammatory process. Therefore, prior as well as concurrent nutrient intake are of importance in determining the outcome of the inflammatory response.

Antioxidants↗

PubMedDate not supplied

Immunonutrition: role of sulfur amino acids, related amino acids, and polyamines.

Pro-inflammatory cytokines mediate widespread changes in protein metabolism. Amino acids released from peripheral tissues fulfill a number of functions. They act as substrate for acute phase protein and immunoglobulin synthesis and, together with polyamines, in the replication of immune cells. Demands for specific amino acids may outstrip the supply from endogenous sources. A number of strands of evidence suggest that sulphur amino acids, and amino acids that are metabolically related to them, may be required in increased amounts. Protein deficiency impairs the acute phase response. However, sulfur amino acid insufficiency compromises glutathione synthesis, to a greater extent than hepatic protein synthesis, in the presence and absence of an inflammatory stimulus. The resulting effect may be compromised antioxidant defences. Functioning of T cells is dependent on intracellular glutathione concentrations and may also be affected by sulphur amino acid insufficiency. It has been suggested that the increased N excretion, which occurs during the immune response, is a reflection of a relative imbalance in the profile of amino acids released from peripheral tissues and the requirements imposed by the synthesis of substances involved in the acute phase response. Phenylalanine, tyrosine, tryptophan serine, and cysteine are released in amounts closest to requirements. Polyamine synthesis may be important for the fidelity of the enhanced level DNA transcription and RNA translation that occurs in response to infection and during tissue repair, gut growth after surgery, and in gut barrier functions. Although synthesized de novo from ornithine, arginine and S-adenosyl methionine (SAM), substantial recycling is a key feature of polyamine metabolism. The recycling may be a reflection of the need to maintain adequate tissue SAM during periods of rapid cell growth. During an immune/inflammatory response the combination of enhanced utilization of cysteine for glutathione synthesis and cell replication may lead to depletion of cellular SAM. A relatively small addition of polyamines to the diet may improve gut-associated aspects of the hosts' antibacterial defenses.

Amino Acids, Sulfur↗