Endotoxin-induced prostaglandin (PGF2α) biosynthesis,fever and miosis in dexamethasonetreated goats

Prostaglandin-releasing, adrenocortical, febrile and miotic responses to endotoxin (ET) (E. coil lipopolysaccharide; 0.25 μg kg^-1) were studied in goats with and without prolonged dexamethasone influence. The i.v. injection of ET induced a three-fold peak elevation in plasma 15-ketodihydro-PGF_2α at 1.5 h post-injection, that is, between the first and second phase of the temperature elevation. During the latter phase, the plasma concentration of this primary PGF_2α metabolite gradually returned to basal level, which implies that the second phase of ET fever is not PG dependent. The PG response exhibited a similar pattern, but was less pronounced in the dexamethasone-ET experiments, where the duration of maximum temperature elevation and of the miosis became shortened by about 20 min, and the typical biphasic pattern of ET fever was no longer seen. The ET-induced rise in plasma aldosterone concentration was completely blocked by dexamethasone. The corresponding rise in plasma cortisol concentration was prevented for 2 h, but was later only partially inhibited in spite of the repeated dexamethasone treatment.