|Budget Amount *help
¥7,200,000 (Direct Cost: ¥7,200,000)
Fiscal Year 1986: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1985: ¥2,400,000 (Direct Cost: ¥2,400,000)
Fiscal Year 1984: ¥4,300,000 (Direct Cost: ¥4,300,000)
According to the current progress of fever studies, it must be considered that febrile response is a part of host defence in living organisms. For understanding of this febrile response, three levels of experimental procedures, which include from in vitro experiment to chronic animal experiment, were used in this project. 1. Slice experiment: Endogenous pyrogen or prostaglandin, hypothesized as a final mediator of fever development, changed predominantly the activity of the temperature-responsive neurons in the POAH region of rats. This PG action did not alter following perfusion of low Ca-hi Mg perfusate. Furthermore, cells in the ventromedial hypothalamic nucleus showed a higher sensitivity to PG than that of the POAH region.
2. Acute experiment on anesthetized animals: Systemic administration of EP or PG changed the activities of the temperature-responsive neurons in lightly urethanized rats, but their behavior of the neurons to EP is not similar to those to PG. The thalamic neurons
in the relay nuclei respond to alterations of envirommental temperature applied to rats, classifing the thalamic neurons into two types by their responding pattern. The POAH region, raphe nucleus in the midbrain and the locus coeruleus in the medulla also modulate the activity of the thalamic neurons responding with skin warming and cooling.
3. Chronic experiment: Rats do not usually produce fever so far. However, if rats are dehydrated for an overnight, rats become to show febrile response to systemic injection injection of pyrogen. This means that the ability to produce EP enhances following dehydration. Rat pyrogen which was prepared from whole blood in sensitized rats with pretreatment of lipopolysaccharide, is able to produce fever not only in rats but also in rabbits. However, the same dose of pyrogen per body weight produced higher fever in rabbits than that in rats. Furthermore, central mechanism of biphasic fever which a large amount of endogenous or exogenous pyrogen induced, was examined in rabbits by injection of indomethacin, thereby indicating that fever patter relates with some structures inside or outside the blood-brain barrier. Less