Differential effect of clofibrate on inflammation-induced alterations in plasma proteins in the rat

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Abstract
Daily i.m. injections of clofibrate begun 6 h before the initiation of inflammation induced by the s.c. injection of turpentine exerted a differential, dose-dependent inhibition of the anticipated acute-phase globulin response. Specifically, clofibrate at 140 mg/kg muted the increase in .alpha.2-macrofetoprotein, but did not affect that of seromucoid or haptoglobin and only transiently inhibited the rise in Cu and the rebound in transferrin. A higher dose, 280 mg/kg, markedly suppressed .alpha.2-macrofetoprotein appearance and the rebound in transferrin, somewhat inhibited the increase in seromucoid and haptoglobin and only transiently affected the rise in plasma Cu; 420 mg of clofibrate/kg very nearly abolished the appearance of .alpha.2-macrofetoprotein, markedly suppressed the transferrin rebound and the increases in seromucoid and haptoglobin and again only transiently affected the increase in Cu. Clofibrate did not diminish the localized inflammatory response, did not cause microscopically detectable liver damage and did not prevent the hypozincemia, hypoalbuminemia and enhanced amino acid uptake by liver usually associated with inflammation. Thus it is unlikely that clofibrate exerted its dose-dependent selective inhibition by muting the initial stimulus or by imparing hepatic metabolism. This seemingly selective action of clofibrate on plasma-protein alterations during inflammation may provide a means of elucidating the function of individual acute-phase globulin during disease. Clofibrate of itself, apart from inflammation, produced decreases in plasma Zn, Cu, transferrin and seromucoid and an increase in hepatic amino acid uptake that were to some extent dependent on the dose of the drug.