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At least 433 records · Page 24Linked to original sources
PubMed1960

Pathogenesis of fever: effects of various endogenous pyrogens upon the level of circulating granulocytes in normal rabbits.

The endogenous pyrogen in the serum or plasma of rabbits 2 hours after the intravenous injection of typhoid vaccine had a marked effect on the circulating leucocytes of normal rabbits. Immediately following intravenous injection there was a brief, but marked, granulocytopenia which was quickly followed by a granulocytosis. Under the same circumstances pooled heterologous serum or plasma from normal rabbits produced no fever or significant change in the level of circulating leucocytes. The cell-free fluid of sterile peritoneal exudates produced a marked leucocytosis without a preceding leucopenia when injected intravenously into normal rabbits. When comparably pyrogenic doses of typhoid vaccine were injected in the same manner no significant change in the level of circulating leucocytes occurred. The relevance of these findings to the pathogenesis of fever is discussed.

Agranulocytosis↗
PubMed1968

Studies on the pathogenesis of fever. XVI. Purification and further chemical characterization of granulocytic pyrogen.

Small quantities of highly purified granulocytic pyrogen have been separated from contaminating proteins by disc electrophoresis in polyacrylamide gel. The biologically active material thus isolated was shown to be electrophoretically homogeneous at pH 9 and pH 3.8. Earlier work on the chemical properties of the pyrogen molecule has been extended to include: (a) estimation of its molecular weight by gel filtration; (b) demonstration of free sulfhydryl groups essential for its biological activity; and (c) evidence that it is not inactivated by exhaustive extraction with ethanolether or n-heptane.

Animals↗
PubMed1970

Studies on the pathogenesis of fever. XVII. The cationic control of pyrogen release from exudate granulocytes in vitro.

Evidence has been presented that the release of active endogenous pyrogen from rabbit exudate granulocytes incubated in isotonic NaCl is a relatively prompt energy-dependent process that is preceded by a rise in intracellular pyrogen, and involves a rise in total intracellular cations and an increased permeability of the cell membranes, but does not require the synthesis of new proteins.

Animals↗
PubMed1977

Differences in pyrogen production by mononuclear phagocytes and by fibroblasts or HeLa cells.

Phagocytosis of bacteria stimulates "professional" phagocytes to produce and release endogenous pyrogen (EP), the protein that mediates fever. To determine whether "nonprofessional" phagocytes also have this capacity, mouse and human fibroblasts and HeLa cells were cultured after ingestion of latex or chicken erythrocytes (CE), and EP release into culture supernate measured by mouse assay. No detectable pyrogen was released by these cell types after phagocytosis, whereas both latex and CE stimulated EP production by cultured mouse macrophages. These studies support the hypothesis that only professional phagocytes of bone marrow origin synthesize EP and induce fever.

Animals↗
PubMed1979

Adherent cell function in murine T-lymphocyte antigen recognition. IV. Enhancement of murine T-cell antigen recognition by human leukocytic pyrogen.

A macrophage-dependent, antigen-specific murine T-cell proliferation assay was utilized to examine the role of soluble products of murine and human adherent cells in the activation of T lymphocytes. Highly purified human leukocytic pyrogen, and supernates from both murine and human mononuclear phagocytes-macrophages stimulated the immune T-cell proliferative response to the multideterminant antigens dinitrophenyl-ovalbumin and keyhole limpet hemocyanin. The implications of these studies and the relationship of leukocytic pyrogen to human lymphocyte-activating factor are discussed.

Animals↗
PubMed2000

Neural route of pyrogen signaling to the brain.

In the pathogenesis of systemic inflammation and fever, peripheral inflammatory and pyrogenic signals gain access to the brain via humoral and neural routes. One of the neural routes is represented by chemosensitive afferent fibers of the abdominal vagus. We summarize our recent studies of the role of the abdominal vagus in fever. We conclude that capsaicin-sensitive fibers traveling within the hepatic vagal branch constitute a necessary component of the afferent mechanism of the febrile response to low, but not high, doses of circulating pyrogens. We speculate that this mechanism is triggered by blood-borne prostaglandins of the E series.

Afferent Pathways↗
PubMed2000

Pyrogen sensing and signaling: old views and new concepts.

Fever is thought to be caused by endogenous pyrogenic cytokines, which are elaborated and released into the circulation by systemic mononuclear phagocytes that are activated by exogenous inflammatory agents and transported to the preoptic-anterior hypothalamic area (POA) of the brain, where they act. Prostaglandin (PG) E2 is thought to be an essential, proximal mediator in the POA, and induced by these cytokines. It seems unlikely, however, that these factors could directly account for early production of PGE2 following the intravenous administration of bacterial endotoxic lipopolysaccharides (LPS), because PGE2 is generated before the cytokines that induce it are detectable in the blood and the before cyclooxygenase-2, the synthase that they stimulate, is expressed. Hence other, more quickly evoked mediators are presumed to be involved in initiating the febrile response; moreover, their message may be conveyed to the brain by a neural rather than a humoral pathway. This article reviews current conceptions of pyrogen signalling from the periphery to the brain and presents new, developing hypotheses about the mechanism by which LPS initiates fever.

Brain↗
PubMed1991

Rapid preparation of pyrogen-free 2H2(18)O for human-nutrition studies.

We describe a compact ultrafiltration system for the removal of pyrogens and bacteria from water labeled with the stable isotopes of deuterium and oxygen-18. The ultrafiltration system is constructed from readily available commercial components and can achieve complete removal of pyrogens and bacteria from 1L contaminated water within 30 min. By use of our procedure, loss of the isotopically labeled water by retention in the filtration system was minimal. The purified water is suitable for both oral and intravenous administration to healthy human subjects participating in nutrition studies.

Deuterium↗
PubMed2000

Can sterile and pyrogen-free on-line substitution fluid be routinely delivered? A multicentric study on the microbiological safety of on-line haemodiafiltration.

BACKGROUND: Microbial contamination is characterized not only by the presence of bacteria, but also by high concentrations of biologically active by-products. They are potentially able to cross ultrafiltration and dialysis membranes and stimulate immunocompetent blood cells to synthesize cytokines. In turn, cytokine induction causes acute symptoms and has been incriminated in the long-term complications of haemodialysis patients. Infusion of large volumes of substitution fluids following ultrafiltration of microbially contaminated dialysis fluids may place patients on on-line therapies at particular risk. METHODS: In this study we evaluated 30 machines with a two-stage ultrafiltration system in routine clinical haemodiafiltration settings in six centres for 6 months. Microbiological safety was assessed monthly and at the last use of the filters by determining microbial counts, endotoxin concentration and cytokine-inducing activity. RESULTS: No pyrogenic episodes were observed during the study period. Double-filtration of standard dialysis fluid (range, <1-895 cfu/ml, 0.0028-4.6822 IU/ml) resulted in sterile substitution fluids with endotoxin concentrations well below the Ph.Eur. standard for haemofiltration solutions (range, 0.0014-0.0281 vs 0.25 IU/ml). Moreover, they did not differ from commercial haemofiltration solutions and depyrogenated saline. Likewise, there was no difference in the cytokine-inducing activity between the solutions tested. The high microbiological quality of the ultrafiltered dialysis fluid, which was in the same range as substitution fluid, translates into both the absence of cytokine induction by dialyser back-transport and a redundant safety mode of the on-line system by a second filtration step. CONCLUSION: On-line HDF treatment can routinely be provided with ultra-pure dialysis fluids and sterile substitution fluids at pyrogen-free levels. The online preparation of substitution fluids thus can be considered microbiologically safe.

Bacteria↗
PubMedDate not supplied

Catheter related bacterial infections mimic reactions to exogenous pyrogens during hemodialysis.

Pyrogenic reactions are characterized by fever, chills, hypotension, or a combination of these developing during or shortly after hemodialysis in a previously asymptomatic patient. The temporal association with treatment implicates exposure of the patient's blood to bacterial pyrogens from contaminated dialysate or a reused dialyzer. Routine body temperature monitoring is recommended to detect these exposures. The current study was prompted by the appearance of several symptomatic febrile episodes in patients who were asymptomatic and afebrile before treatment with high-flux hemodialysis. During a 6 month period, temperatures were measured with a digital oral thermometer before and after 9,605 high-flux hemodialyses in 163 patients. Elevations above 100 degrees F (37.8 degrees C) were observed during or after 33 dialyses in 15 patients. In 18 of these dialyses, the temperature was also elevated before treatment began. Four patients who had no symptoms or fever before dialysis accounted for febrile reactions during 11 of the remaining 15 dialysis treatments. Fever was accompanied by rigors during most of the episodes. Subsequent blood cultures grew Enterococcus faecalis (two), Enterobacter cloacae (two), and Pseudomonas aeruginosa and cepacia (one). All four patients had indwelling silastic double lumen venous catheters (PermCaths), all responded to intravenous antibiotics, and all required eventual removal of the catheter. The apparent precipitation of sepsis by dialysis indicates that shear forces caused by high pulsatile blood flow through the catheter may dislodge organisms that have colonized the lumen. Intraluminal instillation of antibiotics is suggested as a preventative measure.

Adult↗
PubMed2003

Possible relationship between streptococcal pyrogenic exotoxin A and Kawasaki syndrome in patients older than six months of age.

BACKGROUND: We previously investigated antibody titers against four kinds of superantigens [streptococcal pyrogenic exotoxin A (SPEA), streptococcal pyrogenic exotoxin C, toxic shock syndrome toxin-1 and staphylococcal enterotoxin B] in patients with Kawasaki syndrome (KS) younger than 6 months of age and reported a relationship between toxic shock syndrome toxin-1 and KS patients. In this study we have investigated antibody titers in KS patients older than 6 months of age. METHODS: Serum of 81 patients with KS older than 6 months of age, before intravenous gamma-globulin therapy, and 88 normal age-matched children were used in this study. The IgG antibody titers against four kinds of superantigens were measured with an enzyme-linked immunosorbent assay. RESULTS: The KS patients showed significantly elevated mean SPEA titer (P = 0.006) and significantly higher incidence of high SPEA (P = 0.0024) compared with the controls. The SPEA titer in KS patients showed a significant positive correlation with the number of days from onset of illness (P = 0.0002). CONCLUSIONS: The elevated antibody titer against superantigens of KS patients older than 6 months of age was different from that of KS patients younger than 6 months of age. Our results suggest that KS patients' exposure to SPEA occurred a few weeks before the onset of KS. SPEA may be one of the possible etiologic agents of KS among patients older than 6 months of age in Kagoshima, Japan.

Age Factors↗
PubMed1986

Severity of fever in influenza: differential pyrogenicity in ferrets exhibited by H1N1 and H3N2 strains of differing virulence.

Intracardial inoculation of large quantities (200 micrograms viral protein/kg body weight) of infectious or u.v.-inactivated purified influenza viruses into ferrets resulted in a rapid febrile response which was significantly lower for two recently isolated H1N1 viruses, A/USSR/90/77 and A/Fiji/15899/83, than for two virulent clones, 7a and 64c, of the A/Puerto Rico/8/34-A/England/939/69 (H3N2) reassortant virus system. These results, which are in accord with the severity of fever produced by these strains in intranasally infected ferrets, show that influenza virus strains can differ in their capacity to induce fever (probably reflecting a differential capacity to induce endogenous pyrogen from phagocytes) and indicate, since u.v.-inactivated strains are pyrogenic, that this may be due to differences between strains in the nature or amount of certain virion components.

Animals↗
PubMed1990

Comparison of cultured human mononuclear cells, Limulus amebocyte lysate and rabbits in the detection of pyrogens.

Isolated human mononuclear cells exposed to either lipopolysaccharide or Staphylococcus aureus secreted interleukin-1 like material. The secretion was concentration dependent. The minimal detectable level in the test solution of lipopolysaccharide and Staphylococcus aureus was 200 pg/ml and 10(5) cells/ml respectively. The sensitivity and specificity of the Limulus Amebocyte Lysate test, the rabbit pyrogen test and the monocyte test are compared. The monocyte test is proposed as an alternative in-vitro test to the rabbit pyrogen test.

Animals↗
PubMed1983

Interferon-inducing, pyrogenic and proclotting enzyme of horseshoe crab activation activities of chemically synthesized lipid A analogues.

Interferon-inducing, pyrogenic and proclotting enzyme of horseshoe crab activation activities of chemically synthesized lipid A analogues were investigated and compared with the same activities of a natural lipid A. These analogues are nonphosphorylated, C-1 or C-4' monophosphorylated and C-1,4' bisphosphorylated derivatives of beta-1,6-linked D-glucosamine disaccharide possessing both ester-bound and amide-bound fatty acid substituents. Fatty acid substituents of the analogues are tetradecanoyl (C14), (R)-3-hydroxytetradecanoyl (C14-OH) or (R)-3-tetradecanoyloxytetradecanoyl [C14-O-(C14)] groups. The biological activities of the samples were assayed after solubilization with triethylamine and complexing with bovine serum albumin. Interferon-inducing activity was exhibited by both the C-1 monophosphorylated compounds examined. Ester-bound and amide-bound fatty acid substituents of these compounds are both C14 or C14 and C14-OH, respectively. Nonphosphorylated, C-4' monophosphorylated and C-1,4' bisphosphorylated compounds possessing the same fatty acid substituents as those of the C-1 monophosphorylated compounds showed no detectable interferon-inducing activity. C-4' monophosphorylated compounds possessing C14-OH as ester-bound and C14-OH or C14-O-(C14) as amide-bound fatty acid substituents exhibited interferon-inducing activity, but nonphosphorylated compounds possessing the same fatty acid substituents did not. None of the analogues exhibited significant pyrogenicity nor proclotting enzyme of horseshoe crab activation activity under the conditions employed in this study.

Animals↗
PubMed2005

Direct pyrogenic input from prostaglandin EP3 receptor-expressing preoptic neurons to the dorsomedial hypothalamus.

Fever is induced by a neuronal mechanism in the brain. Prostaglandin (PG) E2 acts as a pyrogenic mediator in the preoptic area (POA) probably through the EP3 subtype of PGE receptor expressed on GABAergic neurons, and this PGE2 action triggers neuronal pathways for sympathetic thermogenesis in peripheral effector organs including brown adipose tissue (BAT). To explore pyrogenic efferent pathways from the POA, we determined projection targets of EP3 receptor-expressing POA neurons with a special focus on rat hypothalamic regions including the dorsomedial hypothalamic nucleus (DMH), which is known as a center for autonomic responses to stress. Among injections of cholera toxin b-subunit (CTb), a retrograde tracer, into hypothalamic regions at the rostrocaudal level of the DMH, injections into the DMH, lateral hypothalamic area (LH) and dorsal hypothalamic area (DH) resulted in EP3 receptor immunolabelling in substantial populations of CTb-labeled neurons in the POA. Bilateral microinjections of muscimol, a GABA(A) receptor agonist, into the DMH and a ventral region of the DH, but not those into the LH, inhibited thermogenic (BAT sympathetic nerve activity, BAT temperature, core body temperature and expired CO2) and cardiovascular (arterial pressure and heart rate) responses to an intra-POA PGE2 microinjection. Further immunohistochemical observations revealed a close association of POA-derived GABAergic axon swellings with DMH neurons projecting to the medullary raphe regions where sympathetic premotor neurons for febrile and thermoregulatory responses are localized. These results suggest that a direct projection of EP3 receptor-expressing POA neurons to the DMH/DH region mediates febrile responses via a GABAergic mechanism.

Adipose Tissue, Brown↗
PubMed1990

A study of the pyrogenic actions of interleukin-1 alpha and interleukin-1 beta: interactions with a steroidal and a non-steroidal anti-inflammatory agent.

1. The pyrogenic effects of intravenously administered human recombinant interleukin-1 alpha (IL-1 alpha) and IL-1 beta were studied in the rabbit. 2. Both cytokines produced dose-related increases in body temperature. At all doses studied (100-5000 u kg-1) both cytokines elicited a monophasic increase in body temperature, beginning 15 min and reaching a maximum 45 min after administration. 3. A comparison of thermal response index (TRI2, the magnitude of febrile responses over 2 h obtained by integrating the change in temperature in degrees C against time in hours) values indicated that IL-1 beta (500 u kg-1, TRI2 = 0.69 +/- 0.04, n = 4) was approximately 5 fold more potent than IL-1 alpha (2500 u kg-1, TRI2 = 0.73 +/- 0.07, n = 4, all values are means +/- s.e.means) in elevating body temperature. delta Tmax values for the above doses of IL-1 beta and IL-1 alpha were 0.60 +/- 0.06 and 0.61 +/- 0.03 respectively. When IL-1 alpha and IL-1 beta were heated for 30 min at 60 degrees C prior to administration no biological activity was observed. 4. A cyclo-oxygenase inhibitor, ketoprofen (3 mg kg-1) administered 15 min before either cytokine completely abolished the fever induced by both IL-1 alpha (2500 u kg-1) and IL-1 beta (500 u kg-1). 5. Intravenous administration of the steroidal anti-inflammatory agent dexamethasone (3 mg kg-1) 1 h before either cytokine attenuated the fever induced by IL-1 alpha (2500 u kg-1) and IL-1 beta (500 u kg-1). 6. The effects of ketoprofen and dexamethasone on IL-I pyrogenicity indicate that prostanoids are almost certainly involved in the responses. The different potencies of IL-l alpha and IL-1 beta may be related to their relative ability to stimulate prostanoid biosynthesis.

Animals↗
PubMed1990

Macrophage hyperreactivity to endotoxin induced by streptococcal pyrogenic exotoxin in rabbits.

Pretreatment of rabbits with streptococcal pyrogenic exotoxin (SPE) resulted in an enhancement of their febrile response to subsequent endotoxin challenge. This suggested that SPE may enhance the macrophage capacity to respond to endotoxin in vivo to produce an endogenous pyrogen. It was also demonstrated that peritoneal macrophages derived from SPE-treated rabbits exhibited hyperreactivity to endotoxin in vitro as assessed by endotoxin-induced increase in glucose consumption. These data indicate that SPE has the ability to enhance macrophage reactivity to endotoxin.

Animals↗