Immune system metabolic inflammation

The most important clinical application of glucocorticoids and their semisynthetic analogs is their anti-inflammatory activity, discovered in 1949 by Hench and co-workers. The profound anti-inflammatory effects of glucocorticoids arise from the combined effects of these steroids on both the cellular and molecular mediators of inflammation these effects are separate from the metabolic effects described above and further indication of the widespread diversity of macromolecules to which steroids can bind. Glucocorticoids suppress inflammation at the cellular level by downregulating the concentration, distribution, and function of leukocytes (white blood cells) that profoundly influence inflammation and response to infection within the body (In this way, steroids help to mediate the overlap between the endocrine systems [chapter 5] and the immune systems [chapter 6]). Glucocorticoids also suppress inflammation at the molecule level by suppressing inflammatory cytokines, chemokines, and other molecular mediators of inflammation. 

The adrenocorticosteroids have several important physiologic and pharmacologic functions. The glucocorticoids (cortisol, corticosterone) are primarily involved in the control of glucose metabolism and the body s ability to deal with stress. Glucocorticoids have other attributes, such as their ability to decrease inflammation and suppress the immune system. Mineralocorticoids, such as aldosterone, are involved in maintaining fluid and electrolyte balance in the body. 

Glucocorticoid The general class of steroid agents that affect glucose metabolism and are used pharmacologically to decrease inflammation and suppress the immune system. Principle examples include cortisol and corticosterone. 

Infection and inflammation of tissues have also been shown to alter the activity of CYP450 enzymes in the liver, kidney, and brain of humans. Such reduced activity affects Phase I metabolism of xenobiotics and results in increased toxic effects. In the case of the administration of drugs to combat an infection, these effects can result in toxic side effects from the treatment of the infection. Immune system responses to infection can have a negative effect on CYP450 enzyme metabolism of xenobiotics (see Section 4.12). 

The mechanism of induction of low-grade chronic inflammation that accompanies HF-diet-induced obesity was demonstrated to be dependent on TLR-4. Interestingly, in the absence of TLR-4/CD14 receptor for LPS, no low-grade chronic inflammation and insulin resistance were induced by HF feeding in mice. Recently also TLR-2 and TLR-5 were shown to be involved in the innate immune system activation that is responsible for the inflammation induced after HF diet. These results confirm gut microbiota implication in the onset of metabolic disorders associated with obesity. Moreover, in animal studies at least, this high-fat-induced metabohc endotoxemia and subsequent metabolic disease may be reversed using prebiotic dietary fibers and certain bacterial supplements... 

The tenn corticosteroids refers to steroid hormones secreted by the adrenal cortex. Corticosteroids are involved in a wide range of physiologic systems such as stress response, immune response, and regulation of inflammation, carbohydrate metabolism, protein catabolism, blood electrolyte levels, and behavior. 

AA, EPA, DHA, GLA, DGLA, LXs and resolvins suppress lL-1, lL-2, lL-6, and TNF-a prodnction by T cells (110-112, 149, 176-180). This claim suggests that EFAs/PUFAs and their metabolites function as endogenous anti-inflammatory molecules and regulate immune response and thus are likely to be of benefit in obesity, insulin resistance, atherosclerosis, metabolic syndrome X, type 2 diabetes mellitus, CHD, depression, and Alzheimer s disease that are considered as diseases of low-grade systemic inflammation (1-8, 24, 120). Some beneficial actions of PUFAs in various inflammatory conditions are because of the formation of anti-inflammatory compounds such as lipoxins, resolvins, and neuroprotectin Dl. 

These changes are induced by a complex intercellular signalling system, whose main constituents are inflammation-associated cytokines. Among other functions. Interleukin-1, Interieukin-6 and Tumour Necrosis Factor-a initiate the alteration of protein and amino acid metabolism designed to support the increased demand of amino acids to sustain the immune response. In particular, lnterleukin-6, stimulates the production of hepatic APP. The relationship with the sulphurated amino acids (SAA) will be discussed in the following chapters. 

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