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.

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 DELAYED HYPERSENSITIVITY

1958 ◽  
Vol 108 (6) ◽  
pp. 905-924 ◽  
Author(s):  
Jonathan W. Uhr ◽  
M. W. Brandriss
Keyword(s):  
Guinea Pigs ◽  
Serum Antibody ◽  
Specific Antigen ◽  
Endotoxin Tolerance ◽  
Delayed Hypersensitivity ◽  
Febrile Response ◽  
Protein Antigens ◽  
Skin Reactivity ◽  
Highly Sensitive ◽  
Specific Challenge

Guinea pigs with delayed hypersensitivity to protein antigens show a specific febrile response accompanied by a lymphopenia following injection of a desensitizing dose of specific antigen. No signs of shock are observed in highly sensitive animals following this injection. The response is not prevented in sensitive guinea pigs by inducing endotoxin tolerance or by pretreating with cortisone before specific challenge. Using a suitable antigen in sufficiently sensitive animals as little as 100 µg. can elicit a pronounced febrile response. Injection of a desensitizing dose of antigen specifically abolishes systemic as well as skin reactivity for several days. Normal or hypersensitive (delayed-type) animals passively sensitized with sufficient amounts of serum antibody show hypothermia after specific challenge and may show a delayed type of fatal shock. Differences were noted between their systemic reactivities, however, and the reactivity seen in specifically challenged tuberculous animals.

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.

scholarly journals TOLERANCE TO BACTERIAL PYROGENS

1947 ◽  
Vol 86 (1) ◽  
pp. 29-38 ◽  
Author(s):  
Paul B. Beeson ◽  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Serratia Marcescens ◽  
Passive Transfer ◽  
Characteristic Pattern ◽  
Febrile Reaction ◽  
Febrile Response ◽  
Intravenous Injections ◽  
Daily Dose ◽  
Development Of Tolerance

In a study of the febrile responses of rabbits to repeated intravenous injections of pyrogenic substances from Eberthella typhosa, Serratia marcescens, and Pseudomonas aeruginosa, the following observations were made: 1. A characteristic pattern of response to daily injections of the same dose of pyrogenic material was noted. This consisted of a progressive diminution in febrile response during the 1st week or 10 days, after which an animal responded to each injection with approximately the same degree of fever, even when the injections were continued for several weeks. 2. Animals given injections of the same amount of pyrogenic material at semiweekly or weekly intervals showed some diminution in febrile reaction but the alteration was less pronounced than that in animals injected every day. 3. Pyrogen tolerance appeared to be lost quickly. Animals allowed to rest for approximately 3 weeks reacted to readministration of pyrogen with fever comparable with that which occurred after the first injection. 4. By gradually increasing the size of the daily dose of pyrogen a tolerance could be established such that a reduced, but still considerable, amount of pyrogen caused no fever whatever. 5. Rabbits that had been injected with S. marcescens or Ps. aeruginosa pyrogens showed a diminished febrile response to E. typhosa vaccine. 6. Passive transfer of the unresponsiveness to pyrogens could not be demonstrated. 7. Prevention of temperature elevations during the course of immunization by use of an antipyretic drug did not interfere with the development of tolerance to pyrogens. 8. A series of mechanically induced bouts of fever did not reduce the responsiveness to bacterial pyrogens.

Extract from Coriolus versicolor fungus partially prevents endotoxin tolerance development by maintaining febrile response and increasing IL-6 generation

2019 ◽  
Vol 83 ◽  
pp. 69-79 ◽  
Author(s):  
Tomasz Jędrzejewski ◽  
Jakub Piotrowski ◽  
Małgorzata Pawlikowska ◽  
Sylwia Wrotek ◽  
Wieslaw Kozak
Keyword(s):  
Endotoxin Tolerance ◽  
Coriolus Versicolor ◽  
Febrile Response ◽  
Tolerance Development

scholarly journals STUDIES ON THE PATHOGENESIS OF FEVER

1955 ◽  
Vol 101 (5) ◽  
pp. 519-528 ◽  
Author(s):  
Elisha Atkins ◽  
W. Barry Wood
Keyword(s):  
Critical Role ◽  
Passive Transfer ◽  
Typhoid Vaccine ◽  
Febrile Response ◽  
Bacterial Pyrogen ◽  
The Brain

The rate of clearance of intravenously injected typhoid vaccine was studied in unsensitized, sensitized, and pyrogen-tolerant rabbits by means of a passive transfer technique. The blood of unsensitized rabbits which had not been previously exposed to bacterial pyrogen remained pyrogenic for normal recipients throughout a period of 2 hours following the injection. In contrast, rabbits sensitized by having received either one or two injections of the vaccine at least 3 weeks prior to the experiment cleared their blood of the test vaccine within 30 minutes despite the fact that they exhibit the same febrile response as unsensitized rabbits. After 1 hour, however, a transferable pyrogenic substance was again demonstrable in the sera of this group. Reasons are discussed for believing that this newly appearing substance may be of endogenous origin and may be the factor which directly affects the thermoregulatory centers of the brain. Rabbits which are made tolerant by repeated daily injections of vaccine have a characteristically depressed febrile response. Not only were the blood streams of such animals cleared of the injected vaccine within less than 5 minutes, but samples of their sera obtained 1 and 2 hours after the injection also failed to contain demonstrable quantities of the secondary pyrogen observed in sensitized animals. The latter observation is in keeping with the suggestion that the secondary pyrogen may play a critical role in the production of fever.

Absence of endotoxin fever but not prostaglandin E2 fever in the Brattleboro rat

1982 ◽  
Vol 242 (1) ◽  
pp. R116-R120 ◽  
Author(s):  
P. C. Eagan ◽  
N. W. Kasting ◽  
W. L. Veale ◽  
K. E. Cooper
Keyword(s):  
Prostaglandin E2 ◽  
Arginine Vasopressin ◽  
Bacterial Endotoxin ◽  
Cerebral Ventricle ◽  
Intracerebroventricular Injection ◽  
Brattleboro Rat ◽  
Febrile Response ◽  
Long Evans ◽  
Colonic Temperature ◽  
Lateral Cerebral Ventricle

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.

Role of nitric oxide in tolerance to lipopolysaccharide in mice

2005 ◽  
Vol 98 (4) ◽  
pp. 1322-1327 ◽  
Author(s):  
Mirela B. Dias ◽  
Maria C. Almeida ◽  
Evelin C. Carnio ◽  
Luiz G. S. Branco
Keyword(s):  
Nitric Oxide ◽  
Repeated Administration ◽  
Endotoxin Tolerance ◽  
Genetically Engineered ◽  
No Synthase ◽  
Body Core Temperature ◽  
Febrile Response ◽  
Genetically Engineered Mice ◽  
Inos Inhibitor ◽  
Synthase Inhibitor

The injection of repeated doses of lipopolysaccharide (LPS) results in attenuation of the febrile response, which is called endotoxin tolerance. We tested the hypothesis that nitric oxide (NO) arising from inducible NO synthase (iNOS) plays a role in endotoxin tolerance, using not only pharmacological trials but also genetically engineered mice. Body core temperature was measured by biotelemetry in mice treated with NG-monomethyl-l-arginine (l -NMMA, 40 mg/kg; a nonselective NO synthase inhibitor) or aminoguanidine (AG, 10 mg/kg; a selective iNOS inhibitor) and in mice deficient in the iNOS gene (iNOS KO) mice. Tolerance to LPS was induced by means of three consecutive LPS (100 μg/kg) intraperitoneal injections at 24-h intervals. In wild-type mice, we observed a significant reduction of the febrile response to repeated administration of LPS. Injection of l-NMMA and AG markedly enhanced the febrile response to LPS in tolerant animals. Conversely, iNOS-KO mice repeatedly injected with LPS did not become tolerant to the pyrogenic effect of LPS. These data are consistent with the notion that NO modulates LPS tolerance in mice and that iNOS isoform is involved in NO synthesis during LPS tolerance.

Sign in / Sign up

Export Citation Format

Share Document