scholarly journals STUDIES ON THE PATHOGENESIS OF FEVER

1957 ◽  
Vol 106 (6) ◽  
pp. 787-809 ◽  
Author(s):  
Robert G. Petersdorf ◽  
Willis R. Keene ◽  
Ivan L. Bennett

The "endogenous serum pyrogen" that appears in the circulating blood after a single intravenous injection of endotoxin does not produce leukopenia in normal animals, fails to provoke the local Shwartzman reaction, and elicits no "tolerance" when injected daily. Suppression of the febrile response to endotoxin by prednisone does not prevent the appearance of pyrogen in the blood. Animals given large amounts of endotoxin daily continue to respond with high fevers despite failure of endogenous serum pyrogen to appear in detectable amounts after the first two or three injections. Analysis of the response to daily injections shows clearly that the fever during the first 2 hours after administration of endotoxin is unrelated to levels of endogenous serum pyrogen; in contrast, the magnitude of the fever after the 2nd hour correlates well with endogenous pyrogen in some instances. The leukopenic response to endotoxin could not be correlated with the appearance of endogenous serum pyrogen. The differences between endotoxin and endogenous pyrogen and the similarities between leukocyte extracts (sterile exudates) and endogenous pyrogen are summarized and discussed. Dissociation of the febrile response to bacterial endotoxin and levels of endogenous serum pyrogen are discussed and it is concluded that a mechanism involving both direct and indirect action of endotoxins offers the best explanation for the pyrogenic action of these bacterial products.

1952 ◽  
Vol 96 (6) ◽  
pp. 625-641 ◽  
Author(s):  
Robert A. Good ◽  
Lewis Thomas

Intravenous injection of thorotrast or trypan blue rendered rabbits susceptible to the production of bilateral cortical necrosis of the kidneys by a single intravenous injection of small amounts of meningococcal or Serratia marcescens toxin. This reaction was not produced when thorotrast or trypan blue were injected after toxin had been given. A single intradermal injection of toxin produced hemorrhagic skin lesions resembling the local Shwartzman reaction in rabbits given thorotrast 6 hours previously. These animals also developed bilateral cortical necrosis of the kidneys. When the order of injection was reversed, and thorotrast given after toxin, neither skin nor kidney lesions occurred. The skin and kidney lesions in thorotrast-treated rabbits were, like the local and generalized Shwartzman reactions, completely prevented by treatment with nitrogen mustard, in doses sufficient to produce polymorphonuclear leukopenia. The significance of these reactions, and their relationship to the previously described response to toxin in cortisone-treated rabbits, are discussed.


1953 ◽  
Vol 98 (4) ◽  
pp. 331-348 ◽  
Author(s):  
Morgan Berthrong ◽  
Leighton E. Cluff

Intravenous injection into rabbits of bacterial endotoxins results in an inhibition of migration of leucocytes from the buffy coat of their blood in tissue culture or in "slide cell" preparations. This effect was demonstrable 5 minutes after the intravenous injection and persisted for from 6 to 12 hours after the injection. It is as marked in rabbits receiving only a single intravenous injection of endotoxin as in those previously prepared intradermally and developing a severe local Shwartzman reaction on intravenous injection. The preparation of the skin for the Shwartzman reaction does not in itself result in appreciable changes of leucocyte migration. The production of the effect depends upon some action in vivo, since leucocytes of uninjected rabbits migrate normally from the buffy coat in plasma substrates to which large concentrations of endotoxin are added in vitro. The inhibitory effect, as observed in these experiments, also depends upon the added influence of centrifugation. Leucocytes from a rabbit receiving endotoxin intravenously migrate normally from uncentrifuged lung or spleen fragments and migrate normally in blood on the warm stage prior to centrifugation. Identical centrifugation does not affect leucocytes from uninjected animals. The heparin inhibition of the local Shwartzman reaction does not alter this effect of endotoxins on leucocytes. Its possible role in the production of leucopenia and of the local Shwartzman reaction is briefly discussed.


1995 ◽  
Vol 269 (5) ◽  
pp. R1179-R1182 ◽  
Author(s):  
R. L. Simrose ◽  
J. E. Fewell

Rats have an attenuated or absent febrile response to exogenous pyrogen (e.g., bacterial endotoxin) near term of pregnancy. With the aim of providing insight into possible mechanism(s) of the altered febrile response to exogenous pyrogen, experiments have been carried out on 67 time-bred Sprague-Dawley rats to investigate the febrile response to endogenous pyrogen [i.e., interleukin-1 beta (IL-1 beta)]. On day 13 of gestation, intravenous injection of IL-1 beta produced a significant increase in body temperature with a latency of approximately 30 min and a duration of approximately 120 min. In contrast, on days 17 and 21 of gestation as well as on the day of delivery, intravenous injection of IL-1 beta produced significant decreases in body temperature. Thus rats do not develop fever in response to endogenous pyrogen near term of pregnancy but rather become hypothermic. The mechanism of the altered body temperature response to exogenous pyrogen as pregnancy proceeds remains unknown. We speculate, however, that it most likely lies downstream from the formation of endogenous pyrogen.


1955 ◽  
Vol 102 (3) ◽  
pp. 249-261 ◽  
Author(s):  
Lewis Thomas ◽  
Joel Brunson ◽  
Richard T. Smith

Lesions indistinguishable from those of the generalized Shwartzman reaction occured in rabbits when a single intravenous injection of Gram-negative bacterial endotoxin was accompanied, or followed, by an injection of one of the following synthetic, heparin-like, acidic polymers-sodium polyanethol sulfonate, dextran sulfate, or sodium polyvinyl alcohol sulfonate. These reactions were produced by doses of polymer or of endotoxin which were without demonstrable effect when given singly. Heparin, in those similar to those previously shown to protect rabbits against the lesions of the generalized Shwartzman reaction, prevented the reaction to the combined injection of endotoxin and acidic polymers. Nitrogen mustard, which was previously shown to prevent the lesions of the generalized Shwartzman reaction from occurring after two intravenous injections of endotoxin, had no protective action against the lesions produced by the combined injection of endotoxin and polymer. Cortisone did not affect the reaction to endotoxin and polymer. The role of fibrinogen in the reaction under study is discussed in the paper which follows.


1986 ◽  
Vol 61 (6) ◽  
pp. 2060-2066 ◽  
Author(s):  
A. Morimoto ◽  
T. Ono ◽  
T. Watanabe ◽  
N. Murakami

The effect of endogenous pyrogen (EP, from rabbit) and endotoxin (Salmonella typhosa) on rectal temperature (Tre) was investigated in normal and dehydrated rats of both sexes. Intraperitoneal injection of either EP or endotoxin did not affect body temperature. In addition, no changes in Tre were observed when endotoxin was injected intravenously in normally hydrated male rats, but significant falls in Tre occurred in normal female rats. However, intravenous injection of EP produced fever in both sexes, but females generally showed smaller responses. A second intravenous injection of endotoxin, given 3 days after the first injection, always produced fever in normally hydrated rats. The pattern of this febrile response was monophasic. In contrast to the response in normal rats, intravenous endotoxin produced significant fevers with a biphasic pattern in dehydrated rats of either sex, but the febrile responses of male rats were greater than those of female rats. On the other hand, there were no significant differences between febrile responses to intravenous EP exhibited by normal and dehydrated animals. These results show that rats of both sexes possess physiological mechanisms capable of producing a fever following intravenous injections of EP.


1964 ◽  
Vol 12 (02) ◽  
pp. 452-461 ◽  
Author(s):  
F Rodríguez-Erdmann

SummaryThe generalized Shwartzman reaction (gSr) was produced in pregnant rabbits by means of a single intravenous injection of E.-coli endotoxin. The animals developed a profound and a haemorrhagic diathesis. The haemorrhagic condition is thought to be the result of an acute consumption of the plasma-factors of the coagulation system. The pathogenesis of the gSr is discussed in the light of literature dealing with this phenomenon.


1979 ◽  
Vol 236 (3) ◽  
pp. R184-R187
Author(s):  
N. W. Kasting ◽  
W. L. Veale ◽  
K. E. Cooper

Newborn lambs do not become febrile in response to intravenous (iv) bacterial endotoxin in moderate doses. Newborn lambs were tested to see if they could become febrile to large doses of endotoxin or to endogenous pyrogen. At 5 h of age lambs do not become febrile to relatively large doses of endotoxin or to endogenous pyrogen, but rather become hypothermic. At 32 h and all subsequent times, fevers could be elicited. Onset time of fevers in lambs was short initially and gradually lengthened over 9 days, at which time it was similar to the onset time of the adult fever. With respect to the febrile response, newborn lambs showed varying degrees of tolerance after 10 days of daily injections of endotoxin, as compared to the ewe which becomes tolerant in 2 or 3 days.


1969 ◽  
Vol 130 (1) ◽  
pp. 31-47 ◽  
Author(s):  
Jiři Rotta ◽  
Blahoslav Bednář

Several of the toxic properties of streptococcal mucopeptide have been studied in detail. Intravenous injection of as little as 1 µg of mucopeptide, solubilized by ultrasonic treatment, elicits a reproducible febrile response. Rabbits which are made tolerant to Escherichia coli endotoxin are only partially tolerant to the subsequent injection of streptococcal mucopeptide. Soluble mucopeptide was successfully employed to prepare and provoke the localized Shwartzman reaction. Intravenous injection of 80 µg of solubilized mucopeptide leads to diffuse cellular infiltration as well as focal areas of myocardial necrosis, surrounded by inflammatory cells.


1955 ◽  
Vol 19 (2) ◽  
pp. 181-184 ◽  
Author(s):  
Carl A. Gemzell ◽  
Frank Heijkenskjöld ◽  
Lars Ström

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