Involvement of central action of lipopolysaccharide in pyrogen fever.

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Abstract
To elucidate the mechanisms of fever response by bacterial pyrogen (lipopolysaccharide, LPS), pyrogenicity and Limulus amoebocyte lysate (LAL) gelation activity of CSF withdrawn from febrile rabbits induced LPS i.v. was investigated. One ml of CSF was withdrawn from donor animals 2 h after E. coli LPS i.v. injection at graded doses of 0, 1, 10 and 50 .mu.g/kg; its pyrogenicity was checked by administration into cisterna magna of recipient animals. Pyrogenicity was revealed only in the CSF withdrawn from the group injected with 50 .mu.g/kg of LPS. Differences of both protein content and concentrations of ions (Na, K and Ca) were not obtained among the CSF withdrawn from control and LPS-injected groups. All the above CSF had no LAL gelation activity, but the activity could be detected in the CSF withdrawn from animals injected with a higher dose of LPS (500 .mu.g/kg, i.v.). LAL gelation activity of LPS dissolved in normal CSF was 2 orders less potent in comparison with that of LPS dissolved in saline, which suggested the presence of inhibitor(s) in CSF for LAL assay. Pyrogenicity was not revealed in the CSF withdrawn from hyperthermic rabbits induced by administration of reserpine after pretreatment with a monoamine oxidase inhibitor. The central action of LPS is evidently involved in pyrogen fever. Monoamines are not closely related to pyrogen fever.