Influence of Pregnancy on Plasma Cytokines and the Febrile Response to Intraperitoneal Administration of Bacterial Endotoxin in Rats

2003 ◽  
Vol 88 (6) ◽  
pp. 747-754 ◽  
Author(s):  
Anita E. Fofie ◽  
James E. Fewell
1960 ◽  
Vol 112 (4) ◽  
pp. 619-634 ◽  
Author(s):  
Henry H. Freedman

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.


1960 ◽  
Vol 111 (4) ◽  
pp. 453-463 ◽  
Author(s):  
Henry H. Freedman

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.


1982 ◽  
Vol 242 (1) ◽  
pp. R116-R120 ◽  
Author(s):  
P. C. Eagan ◽  
N. W. Kasting ◽  
W. L. Veale ◽  
K. E. Cooper

Changes in colonic temperature following intracerebroventricular injection (icv) of bacterial endotoxin or prostaglandin E2 (PGE2) were measured in Long-Evans (LE) and Brattleboro (DI) rats. Indwelling cannulas were implanted into the brains of rats for subsequent microinjection into a lateral cerebral ventricle. Microinjection of 1 microgram of bacterial endotoxin into a lateral cerebral ventricle produced a fever in the LE rat but not in the DI rat. Daily injections of 1 microgram of endotoxin icv in the DI rat did not result in a fever. Intraperitoneal injections of 50 micrograms of bacterial endotoxin resulted in a fever in the LE rat, but the DI rat showed no such response. Both groups of animals did produce a fever in response to icv administration of 200 ng of PGE2. The lack of arginine vasopressin in the DI rat may be related to the animal's failure to show a febrile response to endotoxin.


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.


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.


1981 ◽  
Vol 59 (6) ◽  
pp. 613-614 ◽  
Author(s):  
A. V. Ferguson ◽  
W. L. Veale ◽  
K. E. Cooper

The effect of age on the febrile response of New Zealand White rabbits was investigated by administering bacterial endotoxin intravenously to animals from two different age groups. Rabbits greater than 2.0 years of age developed significantly smaller fevers than did animals that were less than 1.0 year old (p < 0.001). The deficit in the febrile response of older animals was specifically related to an absence of the second peak of fever.


1960 ◽  
Vol 199 (5) ◽  
pp. 809-813 ◽  
Author(s):  
John C. Herion ◽  
Richard I. Walker ◽  
Jeffress G. Palmer

Administration of typhoid vaccine or purified bacterial endotoxin produced leukopenia maximal at 50–60 minutes, followed by a second drop or plateau at 120–140 minutes. These changes were parallel to the known biphasic response and were noted in both capillary and venous blood. The initial decrease affects both granulocytes and lymphocytes; subsequent leukocytosis was due to granulocytosis. Anesthesia abolished the febrile response but did not affect the leukocyte changes. Repeated daily administration of endotoxin produced febrile tolerance characterized predominantly by loss of the second peak with shortening of duration of fever. A similar shortening of duration of leukopenia was noted with development of tolerance. Brief monophasic fever and leukopenia also was noted when a second dose was given 6 hours after the first. These observations support the concept of the central role of leukocytes in endotoxin fever, and suggest that changes in the ability of leukocytes to release pyrogen are concerned with the mechanism of febrile tolerance.


1961 ◽  
Vol 113 (6) ◽  
pp. 1115-1125 ◽  
Author(s):  
John C. Herion ◽  
Richard I. Walker ◽  
Jeffress G. Palmer

The febrile response to bacterial endotoxin was measured in rabbits made leukopenic with nitrogen mustard. A striking increase in susceptibility to the lethal effects of endotoxin occurred in severely leukopenic animals. Animals without circulating granulocytes, or with only basophils, developed no significant fever after endotoxin injection. Animals with circulating granulocytes other than basophils exhibited a biphasic febrile response to endotoxin; this response was significantly less in magnitude than that of control animals. Control animals, severely granulocytopenic animals, and animals with no circulating granulocytes other than basophils showed comparable febrile responses to serum pyrogen. These results suggest that granulocytes inactivate endotoxin in vivo and support the hypothesis that leukocyte pyrogen is a necessary intermediate in endotoxin fever. Basophils do not appear to participate in this process. These observations also contradict previous studies that were taken to indicate a normal febrile response to endotoxin in leukopenic animals and suggest that those results are related to the persistence of granulocytes.


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