Acute phase response metabolism

For some vitamins or trace elements, serum measurement is limited in value, especially in seriously ill patients. This is partly a result of the lack of correlation between the amount of nutrient in the plasma compartment with the amount within the intracellular compartment in most body tissue. For example, there may be substantial stores of particular vitamins or trace elements in individual tissue (e.g., vitamin A in the liver), but mobilization into the plasma is affected by the availability of the appropriate binding proteins or by metabolism. Also, there are differences in the content of individual vitamins or trace elements between tissues, and the serum concentration will not reflect these differences. Fur-tliermore, and particularly important, is the fact that the concentration in plasma can alter rapidly when an acute phase response (APR) to trauma or infection leads to redistribution of metals between body compartments there is increased synthesis of metallothionein, leading to the uptake of zinc into the fiver, and increased synthesis of ferritin causing uptake of iron. The result is a fall in plasma concentration of both zmc and iron. These changes in plasma concentration clearly do not reflect changes in whole body status. 

There is evidence for cytokine-mediated effects on the hormones of intermediary metabolism in the acute phase response but it is conflicting. The early work showed that leukocyte supernatants caused insulin and glucagon release in... 

As is also shown in Figure 6.1, an interleukin-1-mediated [29] acute-phase response to many diseases involves a release of copper-thioneine-stored copper from the liver as ceruloplasmin, copper amino-acid complexes, and a copper albumin complex to meet increased metabolic needs for copper, which exceed normal needs, and plasma copper concentrations increase 200-300% above normal, as illustrated in Figure 6.3. The appropriate increase coupled... 

The hepatocytes are the most active sites of protein synthesis, and albumin plays important roles in the transport of bilirubin, anions, fatty acids, several hormones, and xenobiotics. Albumin also is important in determining the colloidal osmotic pressure of plasma and other body fluids. Other proteins synthesized in the liver include the acute-phase response proteins, complement proteins, and the coagulation cascade proteins (see Chapter 8). The levels of plasma proteins reflect the balance between the rates of synthesis, utilization, and degradation. The liver also plays an important role in the metabolism of cholesterol and lipoproteins (see Chapter 9). 

As stated earlier plasma zinc concentration is low in a wide range of conditions (Halstead and Smith, 1970). One effect of stress , mediated by ACTH and cortisol, is to reduce plasma zinc. This is part of the acute phase response to accidental or surgical injury, the effect lasting for several days. Bacterial or viral infections have a similar effect. There is recent evidence that the fall in plasma zinc is part of a complex series of metabolic events induced by the humoral factors such as Interleukin 1 (Dinarello, 1982) which in turn activates interleukin-6 the active factor responsible for induction of liver... 

ACUTE PHASE RESPONSE-INDUCED ALTERATIONS IN MATERNAL AND CONCEPTUS NUTRIENT METABOLISM... 

The acute phase response protein, metallothionein, MT, belongs to a family of low molecttlar weight cysteine-rich proteins that can bind nutritionally important bivalent cations such as zinc and copper, as well as the envirorunental toxicants, cadmittm and mer-ctuy. Two of the MT proteins (MT-1 and MT-2) are widely expressed in the body with highest concentrations in the liver, kidney, intestine and pancreas. The MT-3 isoform is predominantly foimd in brain while expression of the MT-4 isoform has been detected in skin and tongue squamous epithelium and maternal deciduttm. " Postulated functions of MT include protection against heavy metal toxicity, as a contributor to zinc homeostasis and metabolism, and as an antioxidant and flee radical scavenger. 

Sato M, Sasaki M, Hojo H (1993) Induction of metallothionein synthesis by oxidative stress and possible role in acute phase response. In Suzuki KT, Imura N, Kimura M (eds) Metallothionein III. Birkhauser, Basel, pp 125-140 Satoh M, Tsuchiya T, Kumada Y, Naganuma A, Imura N (1993) Protection against lethal toxicity of various anticancer drugs by preinduction of metallothionein synthesis in mice. J Trace Element Exp Med 6 41-44 Schroeder JJ, Cousins RJ (1990) Interleukin 6 regulates metallothionein gene expression and zinc metabolism in hepatocyte monolayer cultures. Proc Natl Acad Sci USA 87 3137-3141... 

Both RBP and TTR have a relatively short half-life ( 0.5 and 2-3 days, respectively) and, therefore, they must be synthesized continuously to maintain normal plasma levels. Plasma retinol, RBP, and TTR are reduced in states of impaired protein synthesis, which may be due to an inadequate intake of protein or energy or to impairments in metabolism. Plasma RBP and TTR are sometimes used as clinical indicators of visceral protein synthesis. During infection and/or inflammation, plasma retinol, RBP, and TTR fall transiently, even though liver vitamin A reserves are adequate, due to altered protein synthesis during the acute-phase response. Because multiple nutritional and metabolic disturbances can lead to a similar decrease in plasma retinol, RBP, and TTR, laboratory values must be interpreted with caution. 

Abstract The diet of industrialised countries is usually rich in amino acids, which are partly used as a source of calories. However, metabolic alterations are observed in diseased patients and a preferential retention of Sulphurated Amino Acids (SAA) occurs during the inflammatory response. It has been demonstrated in an acute sepsis phase model in rats that the metabolism of L-Cysteine (Cys) is modified. Glutathione (GSH) concentration is greater in the liver, kidneys and other organs and Cys incorporation into proteins is higher in the spleen and lungs. In the plasma Acute Phase Proteins are released while Albumin is decreased. The pro-inflammatory cytokines such as Interleukin-1, lnterleukin-6 and TNF-a are the main initiators altering protein and amino acid metabolism. 

Regulates immunes and inflammatory responses stimulates B cell differentiation and antibody production induces expression of hepatic acute-phase proteins regulates bone metabolism... 

Although important links exist between cholesterol metabolism and aspects of cell function, other complicating factors must be considered. Cholesterol metabolism is sensitive to the inflammatory response that accompanies most pathological events. Tumor necrosis factor (TNF) reduces LDL and HDL cholesterol levels and inhibits lipoprotein lipase, resulting in a fall in cholesterol and an increase in triacylglycerol levels. These changes may be perpetuated beyond the acute phase if an inflammatory process is present. Cholesterol metabolism is also sensitive to genetic and environmental factors, which may have independent effects on noncardiovascular disease. As a consequence, the relationship between cholesterol levels and the presence or absence of a disease state must be interpreted with caution. 

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