Induction and Modulation of Acute-Phase Response by Protein Malnutrition in Rats: Comparative Effect of Systemic and Localized Inflammation on Interleukin-6 and Acute-Phase Protein Synthesis ,

Abstract

The acute-phase protein (APP) response is regulated by cytokines such as interleukin-6 (IL-6), interleukin-1 (IL-1) and tumor necrosis factor (TNF), but may also be influenced by malnutrition. The aims of this study were as follows: 1) to determine in rats the effect of a protein-deficient diet on IL-6 mRNA expression in intestine, liver and peripheral blood mononuclear cells (PBMC), and on alpha-1 acid glycoprotein (AGP) and alpha-2 macroglobulin (A2M) serum levels and hepatic mRNA expression; 2) to compare, in protein-deficient rats, the IL-6 and APP responses after a turpentine (TO)- or a lipopolysaccharide (LPS)-induced inflammation; and 3) to determine the effect of a protein malnutrition on IL-6 mRNA expression in rat PBMC treated ex vivo with LPS. Interleukin-6 mRNA was present in intestine and PBMC but not in the liver of malnourished rats, and was absent in any tissue or cells of controls. A2M was present in the serum from malnourished rats but not after refeeding. AGP mRNA expression was not influenced by protein malnutrition. In malnourished rats, IL-6 serum level peaked later than in controls after TO and LPS treatment. In malnourished TO-treated rats, A2M mRNA increased earlier than in controls and remained detectable later than in controls. AGP mRNA expression after TO was not influenced by protein malnutrition. In PBMC of malnourished rats, LPS-induced IL-6 mRNA expression occurred earlier and lasted longer than in controls. Our results indicate that protein malnutrition by itself induces IL-6 and A2M expression, and that it modulates the APP response to inflammation.

Increased globulin and its association with hemorrhagic transformation in patients receiving intra-arterial thrombolysis therapy

“…The cytokines including interleukin-6 (IL-6), interleukin-1 (IL-1), and tumor necrosis factor α (TNFα) can act on the liver and induce the synthesis of positive acute-phase reactants by the liver mediated by acute-phase protein genes [7,11,[15][16][17][18] . Most of these are globulins, including C-reactive protein, α 2 -macroglobulin, prothrombin, fi brinogen, and serum amyloid A (among others), and this might explain the increased serum globulin level in our study.…”

Role of Serum Amyloid A During Metabolism of Acute-Phase HDL by Macrophages

“…In mammals, plasma concentrations of apolipoproteins, in particular apo A-I, decrease significantly, but levels of triglyceride-, phospholipid-, and cholesterol-rich particles are also changed in parallel. 19,21,35,36,57 To study acute inflammation in animals, 2 types of injury are generally used 58 : localized inflammation induced by the formation of a sterile abscess after subcutaneous injection of oils 35,36,59 and systemic inflammation induced by intravenous injection of lipopolysaccharide. 58 Although slight interspecies differences in the inflammatory response may occur between both types of inflammation, 59 rabbits have been proven as a suitable animal model to study inflammation-related changes in lipoprotein and apolipoprotein metabolism 35,36 ; therefore, we decided to use rabbit acute-phase HDL as a source of SAA-containing particles.…”

“…19,21,35,36,57 To study acute inflammation in animals, 2 types of injury are generally used 58 : localized inflammation induced by the formation of a sterile abscess after subcutaneous injection of oils 35,36,59 and systemic inflammation induced by intravenous injection of lipopolysaccharide. 58 Although slight interspecies differences in the inflammatory response may occur between both types of inflammation, 59 rabbits have been proven as a suitable animal model to study inflammation-related changes in lipoprotein and apolipoprotein metabolism 35,36 ; therefore, we decided to use rabbit acute-phase HDL as a source of SAA-containing particles. The enrichment of rabbit HDL with SAA during the acutephase reaction occurs in a similar manner as described for Results shown represent mean values from triplicate dishes and are expressed as apparent particle uptake (expressed as HDL protein that would be necessary to account for the observed tracer uptake; see Methods).…”

Effects of glutamine supplementation on gut barrier, glutathione content and acute phase response in malnourished rats during inflammatory shock

“…The depletion of reduced glutathione content in the mucosa could therefore favor oxidative stress within the mucosa. In addition to the liver, intestine also contributes to the systemic inflammatory response and acute phase proteins expression [10] and this intestinal acute phase response may be influenced by protein malnutrition [11,12] . Although glutamine has traditionally been recognized as a nonessential amino acid, recent studies have demon-strated that glutamine plays a major role in the response to injury [13] , in the enterocyte oxidative metabolism [14] , and in the maintenance of the intestinal epithelium [15,16] .…”