The Experimental Approach to the Mechanism of Fever

Petersdorf, Robert G.

doi:10.1001/archinte.1959.00270060143021

Cited by 16 publications

(8 citation statements)

References 26 publications

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“…Controls exhibited fluctuations in Tr, which were attributed to the normal circadian rhythm seen in chickens, with temperatures being highest during periods of increased activity (Whittow, 1976). The two-step increase in Tr seen in the endotoxin-treated birds was similar to that reported previously in mammals (Petersdorf and Bennett, 1959;Myers et al, 1974). Jordan and Hinshaw (1964) reported that chickens were resistant to the lethal effects of large doses of endotoxin.…”

Section: Discussionsupporting

confidence: 86%

“…Although both peaks in Tr may be caused by endogenous pyrogen (Atkins, 1960), it has been suggested that the first peak in the fever is caused by the direct action of the injected pyrogen on the central nervous ysytem (Petersdorf and Bennett, 1959). The second peak in the biphasic response is generally attributed to the action of an endogenous pyrogen released from granulocytes in the blood that acts upon the hypotiialamus (Petersdorf and Bennett, 1959;Atkins, 1960).…”

Section: Discussionmentioning

confidence: 99%

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Rectal Temperature and Blood Chemical Responses of Young Chickens Given E. Coli Endotoxin

1981

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Two experiments were conducted to investigate the effect of intravenous injections of bacterial endotoxin in broiler chicks. In both experiments 5-weeks-old chicks were given a single intravenous injection of either distilled water (control) or 1 mg/kg Escherichia coli endotoxin (serotype 0.127:B8) in a volume of 1 mg/kg. In Experiment 1 rectal body temperatures were taken every hour for 24 hr postinjection. In Experiment 2, rectal temperatures and blood samples were taken at 3, 6, 9, 12, 15, and 24 hr following the administration of endotoxin. Hematocrits and plasma glucose, protein, sodium, potassium, magnesium, calcium, and inorganic phosphorus were measured at each time interval. Birds receiving endotoxin showed a significant increase in rectal temperature from 2 hr until 17 hr postinjection. The febrile response was biphasic with temperatures peaking at 3 to 5 hr and again at 9 to 12 hr. No significant changes in hematocrits occurred following endotoxin injection. Plasma protein, potassium, and calcium decreased significantly, while glucose increased significantly after endotoxin administration. No significant changes in plasma magnesium, sodium, or inorganic phosphorus were observed in endotoxin-treated chicks.

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Section: Discussionsupporting

confidence: 86%

Section: Discussionmentioning

confidence: 99%

Rectal Temperature and Blood Chemical Responses of Young Chickens Given E. Coli Endotoxin

1981

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“…Petersdorf, Bennett, and Keene (14,15) have suggested that in endotoxin fever the first peak is due to the direct action of the endotoxin on the central nervous system and that the second peak is caused by the mobilization of endogenous pyrogen from the tissues. Manifestly, this hypothesis cannot be applied to the biphasic fevers caused by the injection of endogenous pyrogens which contain no demonstrable endotoxin (9-11, 13, 16).…”

Section: Discussionmentioning

confidence: 99%

Studies on the Pathogenesis of Fever

Bornstein

Bredenberg

Wood

1963

The Journal of Experimental Medicine

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The only method presently available for assaying the potencies of pyrogenic molecules is based on the febrile responses of suitably trained hosts (usually rabbits) to intravenous injections of the pyrogens. A preliminary study of the dose-response curve for rabbit leucocytic pyrogen has revealed a hyperthermic "ceiling" at which there is little sensitivity to dosage (1). A similar ceiling has been noted in the response of rabbits to pyrogenic bacterial endotoxin (2, 3). The bearing of these findings on the accuracy of the assay procedure has already been emphasized (1, 3).The present report deals with a more comprehensive investigation of the febrile response as a function of dosage in the rabbit leucocytic pyrogen system. The quantitative relationships which obtain at relatively low dosages are further defined, the effects of large doses, multiple injections, and constant infusions are described, and the phenomenon of tolerance to leucocytic pyrogen is examined. The possible bearing which these data may have upon the manner in which the thermoregulatory systems of the host respond to endogenous pyrogen is briefly discussed. MethodsThe procedures used (a) in avoiding contamination of reagents and glassware with extraneous pyrogens, (b) in preparing leucocytic pyrogen (LP), (c) in assaying the activity of the pyrogen preparations by intravenous injection of rabbits, and (d) in measuring the febrile responses of the rabbits in arbitrary fever index units were the same as those described in previous publications (1,(3)(4)(5), except for the following:R~ording of Temperature Re.spons=.--For purposes of comparison, fever indices (areas beneath curves in cm ~) were measured by planimetry of both 2 hour (FII~) and 1 hour (FI60) fever curves. Maximum temperature rises in degrees centrigrade (AT) were also tabulated. Continuous Infusions.--Each continuous infusion was injected through an indwelling

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“…The finding that sodium salicylate counteracts a centrally evoked fever is not compatible with the hypothesis that an antipyretic exerts its action by preventing a pyrogen that is circulating in the blood stream from entering the central nervous system. INTRODUCTION A bacterial pyrogen injected intravenously produces a fever which is characterized by two distinct peaks (Petersdorf & Bennett, 1959;Sheth & Borison, 1960;Tully, Gaines & Tigertt, 1965;Weiss, Laties & Weiss, 1967;van Miert & Atmakusuma, 1970). Although both of these peaks may be mediated by endogenous pyrogen (Atkins, 1960), Bennett, Petersdorf & Keene (1957) suggested that the first peak is caused by a direct action of the injected endotoxin on the central nervous system.…”

Section: Indiana Usamentioning

confidence: 99%

Fever produced by endotoxin injected into the hypothalamus of the monkey and its antagonism by salicylate

Myers¹,

Rudy²,

Yaksh³

1974

The Journal of Physiology

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SUMMARY1. A suspension of the killed cell bodies of either E. coli, S. dysenteriae or S. typhosa was micro-injected through cannulae implanted chronically at specific sites within the diencephalon and mid-brain of the unanaesthetized monkey. A biphasic, monophasic or an undifferentiated fever could be induced by each type of micro-organism, but the type of response depended solely upon the locus of injection.2. Although little difference in the potency of the three pyrogens was found, the rise in body temperature was in each instance dependent upon the concentration of the endotoxin. A more intense fever was accompanied by shivering, vasoconstriction of the ear vessels, piloerection and huddling behaviour. Tolerance to the pyrexic effect of repeated injections of endotoxin did not develop.3. The febrile response having the shortest latency, greatest maximum rise in temperature and largest 10-hr fever index was evoked by microinjections into the anterior hypothalamic, preoptic area. The incidence of biphasic fevers was also greater after endotoxin was injected into this same region. Endotoxin given similarly in the posterior hypothalamus or in the mesencephalon had either no effect or produced a smaller elevation in temperature after a longer latency. The distance of an injection site from the coronal plane formed by the optic chiasm and anterior commissure correlated significantly with the latency and magnitude of the temperature change as well as the fever index.4. When given intravenously, endotoxin in a quantity at least 100 times greater was required to evoke a fever similar to that produced when the pyrogen was micro-injected into the anterior hypothalamic, preoptic region. However, a biphasic fever was evoked with a latency of * Present address:

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The Experimental Approach to the Mechanism of Fever

Cited by 16 publications

References 26 publications

Rectal Temperature and Blood Chemical Responses of Young Chickens Given E. Coli Endotoxin

Rectal Temperature and Blood Chemical Responses of Young Chickens Given E. Coli Endotoxin

Studies on the Pathogenesis of Fever

Fever produced by endotoxin injected into the hypothalamus of the monkey and its antagonism by salicylate

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