SEARCH · PubMed Health

Results for “Pyrogens”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 235 records · Page 13Linked to original sources

PubMed1975

The effect of various amine-depleting drugs on the fever response exhibited by rabbits to bacterial or leucocyte pyrogen.

1 The concentration of noradrenaline, dopamine and 5-hydroxytryptamine (5-HT) in the rabbit brainstem was measured during fevers produced by either an injection of bacterial pyrogen (BP) or continuous infusion of leucocyte pyrogen (LP). 2 Both procedures had little effect on the concentration of noradrenaline in the preoptic/hypothalamic area but significantly (P smaller than 0.001) lowered the concentration of noradrenaline in the midbrain and pons/medulla. 3 BP significantly (P smaller than 0.01) lowered the concentration of 5-HT in the preoptic/hypothalamic area but had no effect in the midbrain or pons/medulla, whereas LP significantly (P smaller than 0.01) lowered the concentration of 5-HT in the midbrain and pons/medulla but had little effect in the hypothalamus. 4 The concentration of dopamine throughout the brainstem was little affected by either BP or LP fevers. However the concentration in the midbrain was significantly reduced by LP (P smaller than 0.001). 5 Alpha-Methyltyrosine (200 mg/kg) pretreatment diminished the pyrogenic response to both BP and LP whilst p-chlorophenylalanine (300 mg/kg) slightly enhanced the response to both forms of challenge. 6 Reserpine (1 mg/kg) diminished both types of fever whilst a combination of alpha-methyltyrosine and p-chlorophenylalanine slightly enhanced the fevers produced by either BP or LP. 7 The results obtained are discussed in relation to the mechanisms involved in the production of fever and to the possible function of noradrenaline and 5-HT as thermoregulatory transmitters.

Amines↗

PubMed1993

Effects of pyrogenic immunomodulators on the release of corticotrophin-releasing factor-41 and prostaglandin E2 from the intact rat hypothalamus in vitro.

1. The actions of the following pyrogens: lipopolysaccharide (LPS), polyinosinic:polycytidylic acid (Poly-I:C), human interleukin (IL)-1 alpha and IL-1 beta, human IL-6 and rat interferon (INF) on corticotrophin-releasing factor-41 (CRF-41) and prostaglandin E2 (PGE2) release from the intact rat hypothalamus in vitro have been studied. 2. Rat hypothalami were incubated in vitro in an artificial cerebrospinal fluid. Immunoreactive (ir)-CFR-41 and PGE2 released into the medium were measured by two-site enzyme amplified immunometric assay (EAIA) and radioimmunoassay (RIA) respectively. 3. Human IL-6 (1 to 10,000 IU ml-1) caused a dose-dependent release of irCRF-41, rising to a maximal 3-4 fold increase over basal at the highest dose tested. Human IL-1 alpha (1 to 1000 IU ml-1), human IL-1 beta (1 to 1000 IU ml-1), poly-I:C (10 pg ml-1 to 100 micrograms ml-1) and rat INF (1 to 10,000 IRu ml-1) all failed to alter irCRF-41 release. 4. LPS (1 mg ml-1) caused a 35% decrease in irCRF-41 release; however, over the dose-range of 0.1 microgram ml-1 to 100 micrograms ml-1, LPS failed to alter irCRF-41 release. The decreased irCRF-41 release in response to LPS (1 mg ml-1) was accompanied by a decrease in the subsequent 56 mM KCl stimulation of irCRF-41. 5. Human IL-1 alpha and IL-1 beta (1000 IU ml-1) were able to stimulate the release of irPGE2 from intact hypothalami, causing a 2 fold increase over basal release. Poly-I:C (100 microg ml-1), LPS (0.1 microg ml-1 to 1 mg ml-1), rat INF (10,000 IRu ml-1) and human IL-6 (1 to 10,000 iu ml-1) all failed to alter irPGE2release.6. In conclusion, these results suggest that the in vitro release of CRF-41 and PGE2, in response to pyrogens, are mediated via different cytokines. In view of this it is possible that different cytokines may mediate the temperature, prostaglandin and hypothalamo-pituitary-adrenocortical axis activation seen during pyrogenic stimulation in vivo.

Adjuvants, Immunologic↗

PubMed1984

Renal excretion of prostaglandin metabolites, arginine vasopressin, and sodium during endotoxin and endogenous pyrogen induced fever in the goat.

Responses to intravenous injections of an endotoxin (E. coli-lipopolysaccharide, 1 microgram/kg b.wt.) and endogenous pyrogen were studied in euhydrated and hyperhydrated goats. The biphasic febrile response to the endotoxin was associated with a pronounced increase in the renal excretion of measured prostaglandin (PG) metabolites (11-ketotetranor PGF metabolites). This increase was time-correlated with the elevation of the rectal temperature, and (in hyperhydrated animals) with an inhibition of the water diuresis and an increase in renal excretion of arginine vasopressin (AVP). Other effects of the endotoxin were an immediate depression of renal Na and K excretion followed by the development of pronounced natriuresis, and a reduction of plasma Fe and Zn concentrations. The appearance of the febrile reactions (peripheral vasoconstriction and shivering) was accompanied by miosis. The maximum elevation of the rectal temperature was significantly greater during euhydration than during hyperhydration. Also endogenous pyrogen elicited miosis concomitant with febrile reactions, and an elevation of the renal excretion of PG metabolites which was closely correlated in time with the monophasic febrile response, and (during hyperhydration) with temporary inhibition of the water diuresis and an increase in the renal AVP excretion. However, the responses were much weaker than the corresponding endotoxin effects. No appreciable changes in renal excretion of Na and K were observed in response to the endogenous pyrogen. It is concluded that the observed effects on renal cation excretion were manifestations of direct endotoxin influences on kidney function.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1981

A comparative study on the performance of asbestos-free depth-filters for removal of pyrogens from infusion fluids.

Three asbestos-free depth-filters were compared with traditionally used asbestos-containing depth-filters for chemical integrity, physical integrity and pyrogen retention. With chemical and physical integrity only minor differences between the various filter types were seen. One asbestos-free depth-filter, based on charcoal, showed poor pyrogen-retention; this might be due to a high flow rate used. Asbestos-free depth-filters based on kieselguhr or on a mixture of kaolin and alumina proved to be good alternatives; these filters have proved to be suitable for the removal of pyrogens from electrolyte- or carbohydrate-containing infusion fluids.

Chemical Phenomena↗

PubMed1973

Pyrogen fever and prostaglandin-like activity in cerebrospinal fluid.

1. In the unanaesthetized cat, rectal temperature was recorded and c.s.f. was collected from a Collison cannula implanted into the third ventricle with its opening lying in close proximity to the anterior hypothalamus. Samples of c.s.f. were collected from the same cat, during normal temperature, during fever produced by Shigella dysenteriae injected into the third ventricle and during the fall in temperature which occurred when the antipyretic paracetamol was injected intraperitoneally during the pyrogen fever.2. The samples of c.s.f., when tested on the rat stomach fundus preparation, caused contractions which were not due, or at most to a small degree only, to 5-hydroxytryptamine, as they were resistant to BOL. They were therefore probably due to a prostaglandin-like substance.3. When assayed against PGE(1), the activity of c.s.f. collected from cats when their body temperature was normal corresponded to between 1.3 and 10 ng/ml. The values, whether low or high, rose over 2.5-4 times to between 4 and 35 ng/ml. in c.s.f. collected during pyrogen fever; they were again low, between 1.5 and 6 ng/ml., in samples collected when the fever had been brought down by paracetamol, but rose again with the return of fever.4. The results provide direct evidence for the theory that fever produced by pyrogens results from their ability to increase synthesis and release of prostaglandins, and that antipyretics bring down the fever because they inhibit the increased synthesis.

Acetaminophen↗

PubMed1976

Effects of atropine, injected into a lateral cerebral ventricle of the rabbit, on fevers due to intravenous leucocyte pyrogen and hypothalamic and intraventricular injections of prostaglandin E1.

1. Cholinergic synapses in the hypothalamus may transmit information in those thermoregulatory pathways which function to raise body temperature. The effect of atropine, administered intracranially, on the febrile response to intravenous leucocyte pyrogen or intracranial prostaglandin E1 was therefore examined in conscious rabbits. 2. In rabbits exposed to a thermoneutral environment, micro-injections of PGE1, into the anterior hypothalamus, intraventricular injections of PGE1, and intravenous injection so leucocyte pyrogen all caused fever accompanied by vasoconstriction in the ears and reduced respiratory rate. Intraventricular injection of 200 mug atropine during such fevers attenuated their development. This was due to the activation of heat loss mechanisms through vasodilatation in the ears and an increase in the frequency of respiration. This suggests a similarity in the pattern of neuronal activity evoked by PGE1 and leucocyte pyrogen, at least at the site(s) where atropine directly or indirectly exerted its effect and in the efferent pathways from this site. 3. In rabbits exposed to a cold environment, intraventricular injection of PGE1 caused fever through the activation of shivering accompanied by increased O2 consumption. Intraventricular injection of atropine during the development of fever caused an inhibition of shivering accompanied by increased O2 consumption. Intraventricular injection of atropine during the development of fever caused an inhibition of shievering and a decrease in O2 consumption so that temperature ceased to rise and returned to normal. 4. During fever, reversal by atropine of the increased heat conservation of rabbits in a neutral environment, and of their increased heat production in a cold environment adds further support to the concept that cholinergic synapses provide an important link in central temperature-rasising pathways.

Animals↗

PubMed1977

Comparison of limulus amebocyte lysates and correlation with the United States Pharmacopeial pyrogen test.

Six limulus amebocyte lysate (LAL) preparations obtained from five different suppliers were evaluated for sensitivity, dependability, cost, convenience of use, and correlation with the United States Pharmacopeial (USP) rabbit pyrogen test method. Endotoxins from various gram-negative microorganisms were used for the evaluation. Major differences among the LAL preparations lie in the area of sensitivity. Differences, up to 100-fold, exist in the sensitivity of the various LAL preparations to the same endotoxin. The LAL tests in general were 3 to 300 times more sensitive than was the USP rabbit pyrogen test method. The LAL and the USP rabbit pyrogen test data correlated well when the endotoxin in a relatively pure and undegraded form was examined. However, large discrepancies in correlation were found when partially degraded endotoxins were compared. One LAL preparation responded to both intact and degraded endotoxin, whereas others responded only to intact endotoxin; the latter closely correlated with the febrile response of the rabbit. Therefore, proper selection of an LAL preparation is important for its application in clinical, pharmaceutical, public health, and environmental areas.

Animals↗

PubMed1977

Filtration removal of endotoxin (pyrogens) in solution in different states of aggregation.

Bacterial lipopolysaccharides are recognized as the major cause of pyrogenic reactions from parenteral solutions. Molecular filtration was used to remove these pyrogenic molecules (endotoxins) from contaminated parenteral solutions. Because bacterial lipopolysaccharides can exist in different states of aggregation, depending on the composition of the solution they are suspended in, the full range of possible states of aggregation was examined by using filters with a wide range of pore sizes. Filters of different pore sizes retained endotoxin lipopolysaccharide presumed to be in the vesicle form, the micelle form, or the detergent-solubilized form in aqueous solutions. Endotoxins (pyrogens) were successfully removed from artificially contaminated solutions of concentrated antibiotics by using filters of 10,000-nominal-molecular-weight limit.

Carbenicillin↗

PubMed1995

Detection of bacterial pyrogens on the basis of their effects on gamma interferon-mediated formation of neopterin or nitrite in cultured monocyte cell lines.

In a number of mammalian cell types, pteridine biosynthesis from guanosine 5'-triphosphate and formation of nitric oxide from L-arginine are induced by gamma interferon (IFN-gamma) and bacterial lipopolysaccharide (LPS). We assessed the possibility of using such metabolic alterations for the in vitro detection of pyrogens. Products from gram-negative and gram-positive bacteria and related synthetic compounds were tested for their potential to induce either of these pathways. Stimulation of pteridine biosynthesis was monitored as the formation of neopterin in the human myelomonocytic cell line THP-1. The formation of nitric oxide was determined as nitrite in murine J774A.1 macrophage cultures. The substances tested included toxic and detoxified parts of LPS and lipid A from Escherichia coli, Salmonella typhimurium, Salmonella minnesota, and Klebsiella pneumoniae as well as lipoteichoic acid and toxic shock syndrome toxin 1 from Staphylococcus aureus. Furthermore, two cell wall compounds from Mycobacterium tuberculosis, trehalose 6,6'-dimycolate and N-acetylmuramyl-L-alanyl-D-isoglutamine, which are active components of Freund's adjuvant, were used. When applied as a single stimulus, only the whole LPS molecule potently stimulated neopterin or nitrite formation. Lipid A and products from gram-positive bacteria were weakly active. For neopterin formation, lipid A required the presence of fetal calf serum. Besides detoxified LPS and independently from the presence of serum, all bacterial compounds tested strongly increased the effects mediated by IFN-gamma. Our results show that bacterial pyrogens can be detected by monitoring the formation of neopterin or nitrite. This may provide a basis for the development of an in vitro assay for the detection of pyrogenic contamination with the aim of replacing the currently used animal test.

Animals↗

PubMed1979

Purification and physicochemical and biological characterization of a staphylococcal pyrogenic exotoxin.

A staphylococcal pyrogenic exotoxin was purified and characterized biochemically and biologically. The organism producing the toxin was a group I Staphylococcus aureus strain which was isolated from a vaginal infection of a patient with mucocutaneous lymph node syndrome (Kawasaki's disease). The possible association of the toxin with the disease syndrome is discussed. The toxin was purified from cell-free culture supernatant fluids by means of differential precipitation with ethanol and resolubilization in pyrogen-free distilled water followed by preparative thin-layer isoelectric focusing. The pyrogenic exotoxin produced fevers in both rabbits and mice and enhanced host susceptibility to lethal shock and myocardial and liver damage by endotoxin. Also, the toxin was a potent nonspecific lymphocyte mitogen, stimulating rabbit spleen cells and human cord blood lymphocytes to proliferate. The toxin migrated as a homogeneous protein when tested with sodium dodecyl sulfate-polyacrylamide gel electrophoresis (molecular weight, 12,000) and reisoelectric focusing (pI 5.3). Hyperimmune antisera raised against the purified toxin reacted with ethanol-precipitated toxin, using immunodiffusion to form a single precipitin arc. The toxin was distinguished from other staphylococcal toxins by a variety of methods. The amino acid composition was determined.

Amino Acids↗

PubMed1984

Biological activities of synthetic lipid A analogs: pyrogenicity, lethal toxicity, anticomplement activity, and induction of gelation of Limulus amoebocyte lysate.

Chemically synthesized lipid A analogs were investigated for several endotoxic activities, including pyrogenicity, lethal toxicity, anticomplement activity, and the capacity to gelate Limulus amoebocyte lysate in comparison to natural lipid A. The synthetic preparations contained D-glucosamine or D-glucosamine-beta-1,6-D-glucosamine disaccharide substituted by ester- and amide-bound hydroxylated or non-hydroxylated fatty acids and by phosphate groups in different combinations. Some preparations which were insoluble in water were succinylated and thus rendered more soluble. Strong biphasic pyrogenic responses with a maximal increase in body temperature of 1 to 2 degrees C were obtained with 50 micrograms/kg doses of 3 disaccharide preparations of 15 tested. With two preparations (50 micrograms/kg) moderate pyrogenicity with monophasic fever curves and a maximal temperature increase of about 0.6 degrees C was obtained. Lethal toxicity tests were carried out in galactosamine-sensitized mice. Of 15 synthetic preparations, 4 exhibited lethal toxicity under these conditions. The effective doses of the lipid A analogs in both in vivo tests were, however, several hundred times higher than those of bacterial lipid A. For the activities in vivo, hydroxyacyl residues seemed to be important. Anticomplement activity was demonstrable in seven preparations, one of which expressed an activity comparable to that of lipid A. Preparations containing non-hydroxylated fatty acids seemed to be most active in this test. None of the synthetic preparations was found to exhibit gelation activity for Limulus amoebocyte lysate when tested in doses up to 0.4 micrograms, whereas bacterial free lipid A was active in doses of about 2 pg. None of the monosaccharide derivatives exhibited any of these activities.

Animals↗

PubMed1973

Pyrogenicity and immunogenicity of lipid A complexed with bovine serum albumin or human serum albumin.

The lipid A component of bacterial lipopolysaccharides (endotoxins), when complexed to bovine serum albumin (BSA) or human serum albumin (HSA), was shown to be a potent pyrogen. Furthermore, rabbits could be protected against endotoxin fever by immunization with both lipid A.BSA and lipid A.HSA complexes. The results presented in this paper show that lipid A is responsible for the pyrogenic activity of endotoxins and their ability to induce pyrogenic immunity.

Animals↗

PubMed1987

Responses of baboons to traditionally pyrogenic agents.

It is not clear whether baboons develop fever in response to endotoxin or other pyrogens. We injected various pyrogens intravenously in 12 unrestrained baboons (Papio ursinus) and measured their body temperature using intra-abdominal radiotelemeters. Serum iron concentration was also measured. The baboons developed fever after injection of killed Staphylococcus aureus (5 X 10(7) organisms/kg). No significant fever was measured after injection of lipopolysaccharide (Salmonella typhosa) (0.1, 8, 40, and 100 micrograms/kg), bovine serum albumin (4 mg/kg), killed Salmonella minnesota (5 X 10(7) organisms/kg), and killed Salmonella typhi (5 X 10(7) organisms/kg). A significant decrease in serum iron concentration was found only after injection of S. aureus and lipopolysaccharide, 100 micrograms/kg. The phagocytic synthesis of interleukin-1 following pyrogen stimulation in baboons and some other primates appears to differ from that in man and in nonprimates.

Animals↗

PubMed1976

Propranolol and pyrogen effects of shivering and nonshivering thermogenesis in rats.

Injection of bacterial endotoxin (Piromen) into unanesthetized rats elicited increases in shivering and nonshivering thermogenesis as well as in colonic temperature. In animals exposed to 24-25 degrees C, treatment with propranolol (a beta-adrenergic antagonist) markedly diminished the pyrogen-induced increases in oxygen consumption (heat production) and colonic temperature with little change occurring in shivering activity. In contrast, in rats exposed to mild cold (17-18 degrees C), propranolol did not significantly alter the magnitude of the pyrogen-evoked thermogenesis. Rather in these animals, shivering tended to increase when nonshivering thermogenesis was blocked. These data are interpreted as reflecting differential effects of pyrogen on the pathways controlling the two modes of heat production in the rat.

Animals↗

PubMed1981

Behavioral responses to pyrogen in cold-stressed and starved newborn rabbits.

Starvation for 2 days and a chronic mild cold stress prevented the rises in body temperature that normally occur in newborn rabbits that have been injected with pyrogen (Piromen, 5 mg/kg). Nevertheless, the stressed pups selected significantly warmer positions in a thermal gradient than did saline-injected littermates and thereby raised their body temperatures. Enhanced heat seeking and subsequent fever were also observed in normally fed pups that were incubated at 24 degrees C and had become hypothermic after pyrogen injection. The responses of the pups before they were allowed to thermoregulate behaviorally resemble the types of thermal responses to infection seen in human newborns. The temperature selection of these pups, and others, indicates that pyrogen elevates the set points of newborn rabbits when endothermic fever is attenuated or even absent.

Animals↗

PubMed1988

Further evidence implicating prostaglandin E2 in the genesis of pyrogen fever.

Conscious cats were used to study the effects of endotoxin and interleukin 1 (IL 1) on levels of prostaglandin (PG) E2 and thromboxane (TX) B2 (the stable TXA2 byproduct) in cerebrospinal fluid (CSF) from the third ventricle. Pyrogens were given intravenously or intraventricularly and prostanoids were measured by radioimmunoassay. PGE2 was normally less abundant than TXB2 (mean, 37 vs. 528 pg/ml), and its level increased severalfold during the sustained fever following intravenous endotoxin (bolus) or IL 1 (bolus plus infusion). PGE2 elevation preceded the fever and was maintained thereafter. Likewise, intraventricular pyrogens promoted PGE2 formation, and their effect was also manifest during the latent period of the fever. The PGE2 metabolite, 13,14-dihydro-15-keto-PGE2, was not measurable in CSF from either afebrile or febrile animals. Basal content of PGE2, on the other hand, was higher in animals pretreated with probenecid (30 mg/kg ip or iv; 50 or 100 micrograms ivt), confirming the importance of transport processes in removing prostanoids from brain. Unlike PGE2, TXB2 levels did not change during the fever to intravenous endotoxin. TXB2 rose instead in response to intraventricular endotoxin, although the elevation did not extend beyond fever uprise. Furthermore, a TXA2 analog (ONO-11113;2 or 4 micrograms ivt) had inconsistent effects on body temperature, while a TXA2 antagonist (ONO-11120;2 micrograms ivt) did not interfere with endotoxin fever. These findings strongly support a causative role for PGE2 in the onset and progression of pyrogen fever. No evidence of a similar role was obtained for TXA2.

Animals↗

PubMed1989

Age- and sex-related differences in febrile response to peripheral pyrogens in the rabbit.

A reduced febrile response with aging has been reported in mice, rats, rabbits, squirrel monkeys and man. Young adult male and female rats and rabbits respond differently to pyrogens, but little is known about relative febrile responses in old male and female animals. To further describe the effects of age and sex on fever, we gave intravenous injections of Salmonella typhosa endotoxin (0.05 micrograms/kg) and of endogenous pyrogen (EP) (40 microliters/kg) to old and young, male and female rabbits. Old females did not exhibit smaller fevers in response to endotoxin compared to young females, but both young and old females had smaller fevers than aged and young males. Old male rabbits did not have a decreased febrile response to endotoxin. Old females, but not old males, showed a reduced febrile response to EP, the presumed endogenous mediator of endotoxin fever, when compared to young rabbits. To determine if the reduced febrile responses were due to reduced capacity to generate heat, D-amphetamine sulfate (2 or 5 mg/kg i.v.) was administered, and the resulting hyperthermias indicated that all groups of rabbits, including the aged and young females, were capable of raising body temperature to high levels. Body weight and reduced capacity to produce and retain heat do not contribute to these differences in fever. We conclude that the febrile response is not uniform over age, and that it is also strongly influenced by sex and type of pyrogen.

Age Factors↗

PubMed1972

The influence of pyrogen-induced fever on salicylamide metabolism in man.

Salicylamide is metabolized in man by biotransformation to salicylamide glucuronide, salicylamide sulfate, and gentisamide glucuronide. The metabolites are quantitatively and rapidly excreted in urine. Study of the metabolism of this drug in volunteers during episodes of pyrogen-induced fever shows a significant reduction in the half-life (t(1/2)) of the excretion of the drug metabolites. The proportion of the drug transformed to its major metabolite, salicylamide glucuronide, is significantly reduced by fever, with concomitant increase in the proportion of one or both of the other metabolites. Thus, the pattern of urinary metabolites of salicylamide is altered. The shortened t(1/2) of the metabolite excretion is probably due to increased hepatic and renal blood flow known to accompany pyrogen-induced fever. This concept was supported by the observation that when two subjects were placed in a high-temperature environmental chamber, a condition in which hepatic and renal blood flows are known to diminish, the t(1/2) of salicylamide metabolite excretion actually increased. No simple explanation exists to explain the changed metabolite pattern noted during febrile periods. It is most likely to be due to complex interactions between the direct or indirect effects of the pyrogens and the factors affecting the hepatic biotransformation of drugs.

Adult↗