SUMMARY1. Micro-injections of prostaglandin E1 (PGE1) into the anterior hypothalamus of the rabbit produced fever which was nearly immediate in onset. The prostaglandin sensitive region appears to be identical to that described as being fever sensitive to leucocytic pyrogen.2. Micro-injections of PGE1 into the posterior hypothalamus and midbrain reticular formation of the rabbit did not produce fever.3. The febrile response to PGE1 injected into the anterior hypothalamus was dose dependent over a range of 20-1000 ng.4. Ambient temperature influenced the thermoregulatory mechanism by which PGE1 fever evolved. In the cold, PGE1 fever was due to increased heat production while during heat exposure both evaporative and dry heat losses were reduced without significant changes in heat production. Vasoconstriction, confined mainly to the ears, was effective in producing fever in standard room environments (24-25°C) along with a small increase in heat production.5. The preoptic anterior hypothalamic area retained its thermosensitivity during PGE1 fever; heating this area attenuated, while cooling augmented the fever.6. The results support the view that PGE1 is a mediator of pyrogen induced fever.

SUMMARY1. Control febrile responses to intravenous injections of endogenous pyrogen were determined in groups of rabbits and rats, exposed to their respective thermoneutral ambient temperatures.2. Discrete electrolytic lesions were placed within the confines of the organum vasculosum laminae terminalis (o.v.l.t.) of each species. The fever responses of the animals were remeasured 3 days later, and in every case there was a marked enhancement of the fevers produced, using the same doses of endogenous pyrogen that were used earlier.3. Similar lesions that were placed unilaterally within the preoptic anterior hypothalamic area in groups of control animals, were not effective in enhancing the febrile responses of these animals.4. The course of this lesion-induced fever enhancement in rabbits was studied during the succeeding 3 week period, when it was found to return gradually towards the control levels.5. It is postulated that the o.v.l.t. is involved in some manner in the process whereby circulating pyrogen is translated into a febrile stimulus. Lesions posited within this region are thought to either increase the amount of pyrogen entering the o.v.l.t., or to increase the sensitivity of pyrogen receptor sites within the o.v.l.t.

SUMMARY1. The febrile sensitivity of male Sprague-Dawley rats to microinjections of prostaglandin E1 (PGE) was investigated at three different locations in the rostromedial hypothalamic region. These were the preoptic anterior hypothalamic area (PO-AH), the organum vasculosum laminae terminalis (OVLT) and the rostral third ventricle (3V).2. Stainless-steel cannula guide tubes were implanted in the OVLT region of one group of animals, within the PO-AH area of a second group and into the third ventricle of a third group of rats. After their recovery, the febrile response of each group was tested to a variety of doses of PGE, each administered in a volume of 1 ,P sterile 0-9 % saline, via a sterile cannula inserted into the implanted guide tubes. Metabolic, vasomotor and rectal temperature changes were monitored continuously for the duration of the fevers.3. Surprisingly, not only did the introduction of PGE into the OVLT region produce fevers, but the sensitivity of this region to PGE in the production of fever greatly exceeded that of the PO-AH area and the third ventricle. Fevers produced by microinjection of PGE into the PO-AH and 3V were identical.4. Doses of PGE as low as 0 5 ng injected into the OVLT produced fevers of 0-5 'C. The fever dose threshold for the OVLT region was one-fifth those of the PO-AH area and the 3V, and the slope of the OVLT dose-response curve was twice those of the P0-AH and the 3V dose-response curves.5. This study demonstrates that there is an anatomically distinct, regional sensitivity in the febrile responsiveness to PGE within the hypothalamus. These results are interpreted as evidence that the site of action of PGE in the production of fever is located within or immediately adjacent to the OVLT region, rather than within the medial PO-AH neuropil as has been believed previously.

Some nitric oxide gas (NO) produced in the sinuses and nasal cavity is absorbed before leaving the nose. To measure production and absorption, we introduced NO at different concentrations into one nostril while sampling the NO leaving the opposite nostril with the soft palate closed. The quantity of NO gas produced in six normal subjects (amount leaving plus the amount absorbed) averaged 352 nl/min and was the same at gas flows ranging from 8 to 347 ml/min and at 10 l/min. An absorption coefficient A was calculated by dividing the amount of NO absorbed by the concentration leaving the nose. A ranged from 17 ml/min at a nasal gas flow of 8 ml/min to an A of 24 ml/min at a nasal gas flow of 347 ml/min. The calculated rates of production and absorption did not change when gas flow rate was increased, suggesting diffusion equilibrium. The amount of uptake of NO in the nasal mucosa can be explained by its solubility coupled with tissue and blood reactivity.