In the present study, endogenous pyrogen (EP), prostaglandin E2 or arachidonic acid was injected into the cerebral ventricle to investigate whether central arachidonic acid metabolites are involved in the development of the acute-phase response. The central effects of a cyclo-oxygenase inhibitor, indomethacin, and of a lipoxygenase inhibitor, nordihydroguairetic acid (NDGA), on the acute-phase response induced by an intracerebroventricular injection of EP were also examined. 2. The ventricular injection of EP decreased the plasma concentrations of iron and zinc, while increasing those of copper and fibrinogen and the circulating leucocyte count. However, ventricular injection of prostaglandin E2 affected neither of them, indicating that prostaglandin E2 does not contribute to the acute-phase response production by itself. 3. Both the ventricular injections of indomethacin and NDGA had no effect on the changes in the plasma concentrations of iron, copper and fibrinogen which were induced by ventricular injection of EP. In addition, when arachidonic acid was administered into the cerebral ventricle, the changes in the plasma levels of iron, copper and fibrinogen were not induced. 4. In contrast, EP-induced hypozincaemia was observed upon pre-treatment with NDGA, but not upon pre-treatment with indomethacin. However, plasma zinc increased after the ventricular injection of arachidonic acid. Ventricular injection of EP alone and of EP with NDGA increased the number of circulating leucocytes 8 and 24 h after the ventricular injection, while ventricular injections of arachidonic acid, and of EP with administration of indomethacin induced leucocytosis 8 h after injections. 5. These results suggest that arachidonic acid metabolites do not participate in the genesis of the acute-phase response.(ABSTRACT TRUNCATED AT 250 WORDS)
