Modulation of rat C-reactive protein serum level by dexamethasone and adrenaline-comparison with the response of α2 phase globulin

Abstract

The alpha-2-acute phase globulin (α₂-APG) of the rat is one of the best investigated acute phase proteins. Glucocorticoids as well as catecholamines could be characterized as potent modulators of α₂-APG concentration. The aim of this study was to investigate whether the C-reactive protein (CRP), another acute phase protein important in human medicine, is also influenced by adrenal hormones and if so whether the effects are receptor-mediated or not. Adrenaline and isoproterenol (a β-agonist) increase the blood level of α₂-APG and CRP dose-dependently probably due to a mechanism involved in the sequence of an inflammatory process, too. Dexamethasone administration led to a sigmoidal dose-response curve in the case of α₂-APG whereas a biphasic sinusoidal-like dose-response curve was obtained for CRP. Doses around 0.01 mg/kg (2×10⁻⁸ Mol/kg) increased while doses around 0.1 mg/kg (2×10⁻⁷ Mol/kg) decreased the CRP serum level. By combination of the agonists (adrenaline, dexamethasone) with the respective antagonists (propranolol, a β-blocking agent and RU 38486, a glucocorticoid antagonist) the agonist-induced changes in concentration of CRP and α₂-APG could be suppressed. Therefore it can be assumed that the hormone effects are receptor-mediated ones. The reactions of arthritic or inflamed rats pretreated with RU 38486 indicate a considerable influence of endogenous glucocorticoids on blood levels of acute phase proteins. Taken together, both α₂-APG and CRP are modulated by adrenal hormones. However, while α₂-APG is influenced in a synergistic way by inducing and modulating factors, CRP seems to be induced and modulated by factors acting just in opposite direction. From the results presented it can be concluded that the hypothalamic-pituitary-adrenal axis is involved in inflammatory processes to a greater extent than assumed so far.