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

The acute-phase protein (APP) response is regulated by cytokines such as interleukin-6 (IL-6), interleukin-1 (IL-1) ana tumor necrosis facto r (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 periph eral blood mononuclear cells (PBMC), and on alpha-1 acid glycoprotein (AGP) and alpha-2 macroglobulin (A2M) serum levels and hepatic mRNA ex pression; 2) to compare, in protein-deficient rats, the IL-6 and APP r esponses after a turpentine (TO)- or a lipopolysaccharide (LPS)-induce d inflammation; and 3) to determine the effect of a protein malnutriti on on IL-6 mRNA expression in rat PBMC treated ex vivo with LPS. Inter leukin-6 mRNA was present in intestine and PBMC but not in the liver o f malnourished rats, and was absent in any tissue or cells of controls . A2M was present in the serum from malnourished rats but not after re feeding. AGP mRNA expression was not influenced by protein malnutritio n. In malnourished rats, IL-6 serum level peaked later than in control s after TO and LPS treatment. in malnourished TO-treated rats, A2M mRN A increased earlier than in controls and remained detectable later tha n in controls. AGP mRNA expression after TO was not influenced by prot ein malnutrition. In PBMC of malnourished rats, LPS-induced IL-6 mRNA expression occurred earlier and lasted longer than in controls. Our re sults indicate that protein malnutrition by itself induces IL-6 and A2 M expression, and that it modulates the APP response to inflammation.