ACTIVATION OF ACUTE-PHASE RESPONSES BY INTRAPREOPTIC INJECTIONS OF ENDOGENOUS PYROGEN IN GUINEA-PIGS

The acute-phase reaction (APR)is the concatenation of events that develops in response to infectious or other acute inflammatory stimuli. It includes fever and changes in plasma trace metal and glycoprotein levels. Endogenous pyrogen (EP) is believed to be the mediator of the APR. It acts within the preoptic-anterior hypothalamus (PO) to initiate fever; prostaglandins E (PGE) may modulate tihs action. To determine whether the nonfebrile response to EP also are mediated by the PO and through PGE, guinea pigs were injected bilaterally intra-PO (iPO) with homologous EP (1 .mu.l) or PGE2 (0.1 .mu.g), and their colonic temperatures (Tco) and plasma Fe, Zn, Cu and N-acetylneuraminic acid (NANA) levels were measured. For comparison, EP (2 ml) also was injected i.p. Heat-denatured EP (.DELTA.EP) or pyrogen-free saline (PFS) was the corresponding control. Fevers were induced by IP EP (1.0 .+-. 0.1.degree. C [mean .+-. SD]), iPO EP (1.1 .+-. 0.2.degree. C), and iPO PGE2 (1.4 .+-. 0.2.degree. C); neither .DELTA.EP nor PFS was pyrogenic. Plasma Fe and Zn levels were decreased significantly after IP EP, but unchanged after iPO EP and PGE2. Plasma Cu and NANA levels were elevated significantly following both IP and iPO EP, but not after iPO PGE2. .DELTA.EP or PFS did not cause any changes, by either route. EP-induced fever and rises in plasma Cu and NANA apparently are mediated by the PO, while the decreases of plasma Fe and Zn are direct, peripheral effects. PGE2 appears to be involved only in the central febrile response. Guinea pigs, pretreated with indomethacin (5 mg/kg, IP), and injected iPO with EP or IP with Salmonella enteritidis endotoxin (2 .mu.g/kg) did not develop fever, but exhibited the rise in plasma Cu and NANA.