Development of fever in the newborn lamb

1979 ◽  
Vol 236 (3) ◽  
pp. R184-R187
Author(s):  
N. W. Kasting ◽  
W. L. Veale ◽  
K. E. Cooper
Keyword(s):  
Onset Time ◽  
Bacterial Endotoxin ◽  
Endogenous Pyrogen ◽  
Febrile Response ◽  
Newborn Lamb

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.

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
Keyword(s):  
Intravenous Injection ◽  
Bacterial Endotoxin ◽  
Endogenous Pyrogen ◽  
Febrile Response ◽  
Single Intravenous Injection ◽  
Shwartzman Reaction ◽  
Endogenous Serum Pyrogen ◽  
Indirect Action ◽  
Local Shwartzman Reaction ◽  
Bacterial Products

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.

Pattern differences in experimental fevers induced by endotoxin, endogenous pyrogen, and prostaglandins

1988 ◽  
Vol 254 (4) ◽  
pp. R633-R640 ◽  
Author(s):  
A. Morimoto ◽  
T. Nakamori ◽  
T. Watanabe ◽  
T. Ono ◽  
N. Murakami
Keyword(s):  
Time Course ◽  
Interleukin 1 ◽  
Bacterial Endotoxin ◽  
Endogenous Pyrogen ◽  
Prolonged Time ◽  
Fever Onset ◽  
Long Latency ◽  
Low Concentrations ◽  
High Concentrations ◽  
Experimentally Induced

To distinguish pattern differences in experimentally induced fevers, we investigated febrile responses induced by intravenous (IV), intracerebroventricular (ICV), and intra-preoptic/anterior hypothalamic (POA) administration of bacterial endotoxin (lipopolysaccharide, LPS), endogenous pyrogen (EP), human recombinant interleukin-1 alpha (IL-1), and prostaglandins E2 and F2 alpha (PGE2 and PGF2 alpha). Intravenous LPS, EP, or IL-1 in high concentrations caused biphasic fever. In low concentrations, they induced only the first phase of fever. Latency to onset and time to first peak of fever induced by IV injection of LPS or EP were almost the same as those after ICV or POA injection of PGE2. Fever induced by ICV or POA administration of LPS, EP, IL-1, or PGF2 alpha had a long latency to onset and a prolonged time course. There were significant differences among the latencies to fever onset exhibited by groups that received ICV or POA injections of LPS, EP, or PGF2 alpha and by groups given IV injections of LPS or EP and ICV or POA injections of PGE2. Present observations indicate different patterns of fever produced by several kinds of pyrogens when given by various routes. These results permit us to consider the possibility that there are several mediators or multiprocesses underlying the pathogenesis of fever.

scholarly journals STUDIES ON THE PATHOGENESIS OF FEVER WITH INFLUENZAL VIRUSES

1958 ◽  
Vol 107 (3) ◽  
pp. 383-401 ◽  
Author(s):  
Elisha Atkins ◽  
Wei Cheng Huang
Keyword(s):  
Newcastle Disease ◽  
Polymorphonuclear Leukocyte ◽  
Influenza A ◽  
Passive Transfer ◽  
Endogenous Pyrogen ◽  
Febrile Response ◽  
Essential Step ◽  
Intravenous Inoculation ◽  
Intraperitoneal Inoculation

A substance with pyrogenic properties appears in the blood streams of rabbits made febrile by the intravenous inoculation of the PR8 strain of influenza A and Newcastle disease viruses (NDV). By means of a technique involving passive transfer of sera from animals given virus to recipient rabbits, the titer of circulating pyrogen was found to be closely correlated with the course of fever produced by virus. Certain properties of the pyrogen are described which differentiate it from the originally injected virus and suggest that the induced pyrogen is of endogenous origin. These properties resemble those of endogenous pyrogens occurring in other forms of experimental fever. The source of virus-induced pyrogen is unknown. In vitro incubation of virus with various constituents of the circulation did not result in the appearance of endogenous pyrogen. Granulocytopenia induced by HN2 failed to influence either fever or the production of endogenous pyrogen in rabbits injected with NDV. Similarly, the intraperitoneal inoculation of NDV into prepared exudates did not modify the febrile response. These findings do not lend support to the possibility that the polymorphonuclear leukocyte is a significant source of endogenous pyrogen in virus-induced fever. It is concluded that the liberation of an endogenous pyrogen from some as yet undefined source is an essential step in the pathogenesis of fever caused by the influenza group of viruses.

Observations on the Development of the Febrile Response to Pyrogens in Sheep

1974 ◽  
Vol 46 (5) ◽  
pp. 591-602 ◽  
Author(s):  
Q. J. Pittman ◽  
K. E. Cooper ◽  
W. L. Veale ◽  
G. R. Van Petten
Keyword(s):  
Cell Count ◽  
White Cell Count ◽  
In Utero ◽  
Body Temperatures ◽  
Febrile Response ◽  
Physiological Mechanisms ◽  
Maternal Body ◽  
Newborn Lamb ◽  
Initial Injection ◽  
Bacterial Pyrogen

1. An initial injection of intravenous bacterial pyrogen in newborn lambs failed to produce fever, but did cause a fall in the number of circulating blood leucocytes. 2. A second challenge of bacterial pyrogen in 60-h-old lambs caused fever, whereas other 60-h-old lambs, not previously injected with pyrogen, were unresponsive. 3. Thus the newborn lamb requires sensitization, by exposure to endotoxin, before pyrogen-induced fever can occur. 4. When bacterial pyrogen was injected intravenously into the unanaesthetized foetus in utero, foetal and maternal body temperatures remained unchanged in response to the initial challenge and to one or two subsequent injections of bacterial pyrogen in utero, or in the lamb immediately after birth. In all instances the foetal white cell count fell in the 90 min after the injection. 5. The response to both bacterial pyrogen and leucocyte pyrogen appears to depend upon the maturity of the physiological mechanisms involved in pyrogen fever.

Effect of Age on the Febrile Response of Rats to Endogenous Pyrogen

Gerontology ◽  
1985 ◽  
Vol 31 (6) ◽  
pp. 349-354 ◽  
Author(s):  
Rosalie Tocco-Bradley ◽  
Rebecca Singer ◽  
Matthew J. Kluger ◽  
Carol A. Kauffman
Keyword(s):  
Endogenous Pyrogen ◽  
Febrile Response ◽  
Effect Of Age

Body temperature response to IL-1 beta in pregnant rats

1995 ◽  
Vol 269 (5) ◽  
pp. R1179-R1182 ◽  
Author(s):  
R. L. Simrose ◽  
J. E. Fewell
Keyword(s):  
Body Temperature ◽  
Intravenous Injection ◽  
Interleukin 1 ◽  
Temperature Response ◽  
Sprague Dawley ◽  
Endogenous Pyrogen ◽  
Febrile Response ◽  
Pregnant Rats ◽  
Sprague Dawley Rats ◽  
Near Term

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.

scholarly journals STUDIES ON THE PATHOGENESIS OF FEVER WITH INFLUENZAL VIRUSES

1958 ◽  
Vol 107 (3) ◽  
pp. 415-435 ◽  
Author(s):  
Elisha Atkins ◽  
Wei Cheng Huang
Keyword(s):  
Influenza A ◽  
Critical Factor ◽  
Blood Stream ◽  
The Other ◽  
Bacterial Endotoxin ◽  
Typhoid Vaccine ◽  
Endogenous Pyrogen ◽  
Cross Tolerance ◽  
Virus Tolerance ◽  
Production Tolerance

Tolerance to the pyrogenic action of intravenously injected virus has been studied in rabbits given either PR8 strain of influenza A virus or Newcastle disease virus (NDV). The following findings suggest that the capacity of the animal to release an endogenous pyrogen is a critical factor. (a) Viruses produce fever by the release of endogenous pyrogen. (b) Tolerance to the pyrogenic effect of reinjected virus is associated with a decrease or absence of endogenous pyrogen production. (c) Tolerance to virus fever may be induced by the prior injection of endogenous pyrogen. (d) Cross-tolerance has been demonstrated between virus and bacterial endotoxin (typhoid vaccine), both of which cause the release of endogenous pyrogen. A difference has been noted in the mechanism of tolerance to successive injections of virus and of bacterial endotoxin. Repeated injections of endotoxins bring about an accelerated clearance of these substances from the blood stream with the result that there is a diminished stimulus to endogenous pyrogen production. Tolerance to virus, on the other hand, is unaccompanied by changes in the rate at which virus disappears from the circulation. It is postulated that circulating endogenous pyrogen, induced by the injection of a number of pyrogenic agents including viruses, temporarily suppresses the further release of endogenous pyrogen and thereby contributes to virus tolerance.

scholarly journals FURTHER STUDIES ON PASSIVE TRANSFER OF TOLERANCE TO PYROGENICITY OF BACTERIAL ENDOTOXIN

1960 ◽  
Vol 112 (4) ◽  
pp. 619-634 ◽  
Author(s):  
Henry H. Freedman
Keyword(s):  
Direct Action ◽  
White Blood Cells ◽  
Test Dose ◽  
Blood Stream ◽  
Passive Transfer ◽  
Bacterial Endotoxin ◽  
Second Phase ◽  
Normal Numbers ◽  
Febrile Response ◽  
Long Term Treatment

The effect of various schedules for inducing tolerance to bacterial endotoxin in donor rabbits upon suitability for demonstration of passive transfer of tolerance to pyrogenicity in normal recipients has been investigated. Long-term treatment of donors, through 5 weeks, is no more effective than a brief series of injections, adding further evidence that tolerance is not attributable to specific antibody to the endotoxin. Qualitative differentiation of the febrile pattern of passively tolerant recipients from that seen in control animals depends upon the magnitude of the test dose of pyrogen. Passively tolerant rabbits respond to endotoxin with an acute leucopenia equivalent to that seen in controls suffering a full biphasic fever. Animals given daily injections of endotoxin continue to show the acute leucopenia, despite the early modification of the course of fever characteristic of endotoxin tolerance. The assumption that the leucopenia reflects damage to the leucocytes, with release of endogenous pyrogen, is not consistent with these findings. Rabbits rendered leucopenic by nitrogen mustard and then given endotoxin exhibit a rapidly developing fever of greater than normal intensity, the exaggeration of the febrile response being proportional to the severity of the induced leucopenia. The implications of these findings for the pathogenesis of endotoxin-induced fever are discussed. The evidence supports the hypothesis that endotoxin produces fever by direct action rather than by release of endogenous leucocytic pyrogen. It is postulated that the lesser fever, in animals having normal numbers of circulating leucocytes, reflects a limitation of available endotoxin by the known rapid sequestration in the white blood cells at the time of the acute leucopenia. It is further suggested that the biphasic febrile response of the normal rabbit results from reinoculation of the blood stream by the temporarily sequestered endotoxin, the RES of the tolerant animal clearing the released endotoxin at a rate sufficient to prevent triggering the second phase of fever.

scholarly journals PASSIVE TRANSFER OF TOLERANCE TO PYROGENICITY OF BACTERIAL ENDOTOXIN

1960 ◽  
Vol 111 (4) ◽  
pp. 453-463 ◽  
Author(s):  
Henry H. Freedman
Keyword(s):  
Endotoxin Tolerance ◽  
Passive Transfer ◽  
Bacterial Endotoxin ◽  
Febrile Response ◽  
Highly Sensitive ◽  
Altered Response ◽  
Prior Administration

The typical febrile response of normal rabbits given bacterial endotoxin intravenously may be modified by prior administration of plasma or, less effectively, serum of endotoxin-tolerant donors. This altered response is characterized by disappearance of the second rise in fever and by a striking reduction in fever index. It thus resembles the course of fever shown by rabbits made tolerant to endotoxin by one or more previous daily doses. This transfer of tolerance by plasma or serum depends critically upon the manner in which tolerance is induced in the donors. The plasma of donor rabbits made tolerant, then given an RES-blocking dose of carbon, still confers tolerance upon normal recipient rabbits. Such donors have lost their tolerance and are highly sensitive to endotoxin at the time their blood is taken. The implications of these findings for endotoxin tolerance and for transfer of this phenomenon are discussed. The evidence is consistent with the hypothesis that both tolerance and its transfer are based upon RES function and are independent of antibody.

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