Abstract
How does the LPS-pyrogen act on the nervous system was analyzed by the Limulus test (pyrogen test) for endotoxin in blood plasma. A cell lysate prepared from amoebocytes of Limulus polyphemus is an extremely sensitive indicator for the presence of endotoxin (LPS-pyrogen) . The state or grade of gelation reaction characteristic of a quantity of endotoxin in plasma is dependent on the concentration of clottable protein in the amoebocyte lysate and endotoxin in the assay mixture. In intact rabbits, gelation reaction for endotoxin in blood plasma during fever induced by LPS-pyrogen injected intravenously was gradually diminished in the time course, though higher temperature in rectum was still kept. And the simultaneous detection of endotoxin in the liquor in central nervous system, the result of the gelation reaction was almost negative. On the contrary, gelation reaction tested in liquor during high fever induced by the lateral ventricular as well as by the subdural administration of LPS-pyrogen was strong positive, but was almost negative in blood plasma. These results suggest that LPS-pyrogen has a strong effect directly on the central thermoregulatory mechanism if it is administered in central nervous system, but LPS-pyrogen itself does not pass through the blood brain barrier. The first and the second peak of the biphasic response to intravenous or intraventricular administration of LPS-pyrogen might be mediated by both exogenous and endogenous pyrogen which were discussed from the results in the present investigation.