THE EFFECT OF PREDNISOLONE AND A PROTEIN-DEFICIENT DIET ON PLASMA-ALBUMIN AND FIBRINOGEN IN A TURPENTINE-INDUCED ACUTE-PHASE REACTION IN RATS

The acute-phase reaction (APR) that follows inflammation is characterized by profound metabolic changes such as hypoalbuminemia, which is frequently aggravated by malnutrition; and hyperfibrinogenemia. Because some of these changes are mediated by cytokines, corticosteroids that are known to suppress cytokine production might be expected to alleviate the course of the APR. In the present study, for 3 weeks rats were fed (I) a standard diet (25% protein), (2) a protein-deficient diet (5% protein), or (3) a standard diet supplemented by treatment with intraperitoneal prednisolone (7.5 mg twice daily starting 3 days before and throughout the experiment). Changes in plasma albumin, fibrinogen, and total protein levels were measured 0, 1, 3, and 8 days after turpentine was injected subcutaneously. Albumin and fibrinogen were immunohistochemically stained in the liver 0, 3, and 8 days after injection. Plasma albumin decreased by roughly 50% in all three groups, and reached a nadir on day 3. Fibrinogen peaked by day 1 in all animals and fell gradually thereafter. The total protein concentration, which was higher with prednisolone, remained unchanged in all three groups. The level of immunostainable liver albumin was initially reduced In malnourished rats. It further diminished in the majority of hepatocytes after administration of turpentine in all groups. Although few hepatocytes stained positive for fibrinogen before the onset of inflammation, uniform increase in immunostaining occurred by day 3 in all rats regardless of treatment. Neither prednisolone nor malnutrition substantially altered the decrease in plasma albumin and the simultaneous increase in fibrinogen in a turpentine-induced APR. The mechanisms regulating the APR appear to be so secure that even massive interventions, such as steroid treatment and malnutrition, are unable to alter the course of the APR.