THE EFFECTS OF PERIODIC CHALLENGE ON THE RESPONSE OF α₂-AP GLOBULIN AND OTHER ACUTE-PHASE REACTANTS OF RAT SERUM TO TISSUE INJURY

Abstract

The effects of periodic challenge with turpentine on the concentration of the acute-phase reactants of serum were studied in young, adult, male Sprague–Dawley rats. The initial injection of the phlogogenic agent was followed by rapid and significant increases in the concentrations of plasma fibrinogen, total serum glycoprotein, serum complement, and the α2-AP globulin and seromucoid fractions. Variable response patterns were observed on subsequent challenges and in the intervals between. The conclusion was drawn that the acute-phase reactants of serum do not respond in a uniform manner to repeated challenge with a phlogogenic agent, and by inference their synthesis must be regulated by several different mechanisms.

A simple inflammation model that distinguishes between the actions of anti-inflammatory and anti-rheumatic drugs

“…This lack of change, or down-regulation of response, during the secondary phase could be caused by a variety of factors: release of cytokine inhibitors, reduced release of cytokines or the liver synthesis of the proteins reaching a maximal level. The phenomenon of down regulation of APP synthesis has been investigated by other researchers and has been seen to occur in animals where repeat injection of the same irritant elicits a reduced reaction [28][29][30]. In the clinic, the plasma levels of CRP in arthritic patients has been shown to correlate to the state of the disease, the secondary phase of adjuvant does not reflect this and is therefore not an appropriate model to use to study the effects of drugs on APP levels.…”

The influence of glucocorticoid on the fibrinogen messenger RNA content of rat liver in vivo and in hepatocyte suspension culture

“…An elevated plasma concentration and an enhanced hepatic synthesis of fibrinogen have been observed after exposure to a variety of noxious stimuli or tissue injuries (Weimer & Humelbaugh, 1967;Kampschmidt & Upchurch, 1974;Koj, 1974). Since the plasma concentrations of the adrenal-cortical hormones are increased in all these 'stress' conditions, these hormones have been thought to have a key role in the regulation of the fibrinogen synthesis.…”

“…concentration of fibrinogen increases during the acute-phase response as a result of enhanced synthesis in liver (Weimer & Humelbaugh, 1967;Kampschmidt & Upchurch, 1974;Koj, 1974), little is known about the molecular regulatory mechanism of the fibrinogen biosynthesis in the liver. Previously, using a cDNA probe specific for fibrinogen-polypeptide mRNA, we have demonstrated that the regulation of fibrinogenpolypeptide synthesis in vivo after inflammation (Princen et al, 1981b), after partial hepatectomy and surgical trauma , or in developing organs , occurs via modulation of the contents of mRNA species coding for fibrinogen polypeptides.…”

The Pharmacological Properties of Seclazone (7-chloro-3,3a-dihydro-2H, 9H-isoxazolo [3,2-b] [1,3] benzoxazin-9-one) A New Anti-Inflammatory Agent

“…It has previously been shown that plasma fibrinogen levels are markedly increased and serum albumin/globulin ratios are inverted in adjuvant-induced polyarthritis in rats (6,8,13,18). Oral administration of seclazone in effective dosage maintained both plasma fibrinogen levels and serum albumin/globulin ratios at approximately normal levels.…”