Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Pyrogens”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

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

At least 595 records · Page 33Linked to original sources
PubMed2000

Vagotomy attenuates the behavioural but not the pyrogenic effects of interleukin-1 in rats.

Vagal afferent signals, have been implicated in cytokine mediated interactions between the periphery and the central nervous system. Studies in experimental animals have shown that cytokine induced activation of brain mediated responses to infection such as fever, sickness behaviour and pituitary-adrenal activation, are inhibited by subdiaphragmatic vagotomy. We have previously proposed that the peripheral signal to the brain in fever is of a humoral nature while others have suggested that either neural afferents or a mixture of both humoral and neural signals may be involved. The objective of the present study was to examine further the role of vagal transmission, in mediating the febrile response to a systemic injection of IL-1beta in rats and to compare this with changes in social exploration behaviour. Intraperitoneal injection of IL-1beta (1.0-30.0 microg/kg) inhibited social exploration in rats and this was attenuated in vagotomized animals. Injection of increasing concentrations of IL-1beta (0.1-1.0 microg/rat) induced significant (P<0.001) increases in core body temperature. However, in contrast to effects on social exploration, the increase in temperature was not inhibited by vagotomy at any of the doses used. These observations demonstrate a dissociation between the two brain mediated events, one of which is dependent on the integrity of the vagus nerve (social exploration) while the other (fever) is apparently generated by different mechanisms which may include circulating pyrogens.

Animals↗
PubMedDate not supplied

The pyrogenic and mitogenic actions of interleukin-1 are related.

Our present understanding of the pathogenesis of fever is that host macrophages, following activation by an appropriate stimulus such as Gram-negative lipopolysaccharide (LPS) immune complexes, or primed lymphocytes in the presence of specific antigen, synthesize and release endogenous pyrogen (EP). EP is carried in the blood circulation to the hypothalamic area of the brain where its action, involving a protein synthetic step, results in an increase of the level at which body temperature is maintained. Recently, it was shown that EP is very similar and possibly identical to another macrophage mediator previously called lymphocyte activating factor and now known as interleukin-1 (IL-1) which, in conjunction with lectin or specific antigen, induces clonal expansion of T lymphocytes. We show here that murine T-cell proliferation in response to IL-1 in vitro is greatly increased when the cells are exposed to a temperature typical of fever and that injection of the same IL-1 causes fever in mice. If this relationship exists in vivo, the resulting facilitation of a T-cell-dependent immune response may well confer survival value and contribute to the evolutionary conservation of fever--a phylogenetically ancient response to infection.

Animals↗
PubMed2002

Association of pyrogenic exotoxin genes with pharyngitis and rheumatic fever/rheumatic heart disease among Indian isolates of Streptococcus pyogenes.

AIM: To monitor the presence of various pyrogenic exotoxin genes in strains of Streptococcus pyogenes isolated in India. METHODS & RESULTS: Isolates recovered from pharyngitis (52) and rheumatic fever (RF)/ rheumatic heart disease (RHD) (8) patients were analysed for the presence of toxin genes, speA, speB and speF, by PCR. The specificity of the products was confirmed by restriction enzyme digestion and Southern hybridization. Among the 60 isolates studied, the incidence of speA, speB and speF were 5(8.3%), 56(93.3%) and 53(88.3%), respectively. The expression of these genes was established in representative isolates by RT-PCR. CONCLUSIONS: Comparative analysis of frequency of the speA, speB and speF genes, among pharyngitis and RF/RHD associated isolates, showed higher incidence in RF/RHD (25%, 100%,100%) as compared to pharyngitis patients (5.8%, 92.3%, 86.5%), respectively. SIGNIFICANCE OF STUDY: The presence of the speA gene, which is usually associated with scarlet fever or toxic shock-like syndrome, within few Indian isolates may be indicative of new virulent strains circulating within the Indian community. High distribution of toxin genes among RF/RHD compared to pharyngitis isolates indicate their possible role in increased virulence.

Adolescent↗
PubMed1992

Different receptor mechanisms mediate the pyrogenic and behavioral effects of interleukin 1.

Interleukin 1 (IL-1) is a cytokine released during immune activation that mediates the host's response to infection and inflammation. Peripheral and central injections of IL-1 induce fever and sickness behavior, including decreased food motivation and reduced interest in social activities. To determine the receptor mechanisms responsible for these effects, rats were injected with IL-1 receptor antagonist (IL-1ra), an endogenous cytokine that acts as a pure antagonist of IL-1 receptors. IL-1ra blocked the increased body temperature and oxygen consumption induced by injection of recombinant human IL-1 only when both cytokines were administered i.p. In contrast, i.p. or intracerebroventricular administration of IL-1ra blocked the depressive effect of IL-1 beta on food-motivated behavior and social exploration when this cytokine was administered by the same route as the antagonist. In addition, intracerebroventricular IL-1ra blocked the reduction in social exploration produced by i.p. IL-1 beta but had only partial antagonist effects on the decrease in food-motivated behavior induced by i.p. IL-1 beta. In each case, the dose of IL-1ra was 100- to 1000-fold in excess of the biologically active dose of IL-1. These results suggest that the receptor mechanisms that mediate the behavioral and pyrogenic effects of IL-1 are heterogeneous.

Animals↗
PubMed1992

Interleukin 1 receptor antagonist blocks somnogenic and pyrogenic responses to an interleukin 1 fragment.

Previously it was shown that human interleukin 1 (huIL-1) and a huIL-1 fragment, huIL-1 beta 208-240, are somnogenic and pyrogenic in rabbits. However, the amino acid sequences for IL-1 are species-specific and it was unknown whether rabbit (rb) IL-1 beta 208-240 and rat (rt) IL-1 beta 208-240 were active in their respective species. Furthermore, it was unknown whether these fragments elicited their effects via the IL-1 receptors. Two doses of rbIL-1 beta 208-240 (6.0 and 12.0 nmol) were intracerebroventricularly administered to rabbits. The 6.0-nmol dose had little effect, whereas the 12.0-nmol dose greatly increased non-rapid-eye-movement sleep across a 6-hr recording period and induced a febrile response. Rats injected intracerebroventricularly with rtIL-1 beta 208-240 at dark onset responded to three doses of the peptide (1.2, 2.4, and 4.8 nmol). The 1.2-nmol dose did not greatly affect sleep but did induce a moderate febrile response. The 2.4- and 4.8-nmol doses increased non-rapid-eye-movement sleep across the 12-hr recording period. Maximal brain temperature elevations relative to controls after the 2.4- and 4.8-nmol doses of the peptide were 0.9 +/- 0.2 degrees C and 0.7 +/- 0.2 degrees C, respectively. These responses in both rabbits and rats were completely blocked or significantly attenuated when the animals were pretreated with an IL-1 receptor antagonist. These results suggest that the biological activities of IL-1 beta 208-240 are mediated via the IL-1 beta receptors.

Amino Acid Sequence↗
PubMed1967

An assay method for leukocyte pyrogen.

A method for assaying leukocyte pyrogen is described which is shown to remain valid despite the presence of very large amounts of bacterial endotoxin. It uses a combination of two procedures to inactivate endotoxin: incubation in normal rabbit plasma for 24 hr at 37 degrees C, and injection into rabbits rendered refractory to endotoxin. The validity of the assay was confirmed by formal statistical methods. A simplified assay method is also described which lacks full statistical validity, but is more suitable for routine use.

Animals↗
PubMed1977

The release of an endogenous pyrogen from guinea pig leukocytes in vitro: a new model for investigating the role of lymphocytes in fevers induced by antigen in hosts with delayed hypersensitivity.

Guinea pig periotoneal exudate (PE) cells incubated overnight in vitro with heat-killed Staphylococci released an endogenous pyrogen (EP) that could be assayed by intravenous injection in rabbits. The febrile responses were linearly related to the dosage of EP over an eightfold range. PE cells derived from guinea pigs with delayed hypersensitivity (DH) to bovine gamma globulin (BGG), also released EP when incubated with antigen in vitro. This reaction was specific and did not occur withe PE cells from normal or complete Freund's adjuvant-sensitized guinea pigs. Studies indicated that monos and/or polymorphonuclear leukocytes rather than lymphocytes were the source of EP. However, when incubated with BGG and sufficient dosages of BGG-sensitized lymphocytes, normal PE cells released EP over a 42 h period. These results suggest that antigen stimulates specifically sensitized lymphocytes to release an agent (perhaps a lymphokine) that activates phagocytic cells to release EP. This model offers unique advantages for investigating in vitro the role of the lymphocyte in antigen-induced fever in DH as well as the relationship of this lymphocyte-induced activity to other known biologic activities mediated by antigen stimulated lymphocytes.

Animals↗
PubMed1980

Release of endogenous pyrogen-activating factor from concanavalin A-stimulated human lymphocytes.

Evidence is presented that the mitogen concanavalin A stimulates human lymphocytes to produce a nonpyrogenic lymphokine (LK) that is capable of activating human monocytes but not granulocytes to produce endogenous pyrogen (EP) in vitro. The potency of this preparation should facilitate further studies to purify and characterize this agent and determine its relation to other know LK. It seems likely that this factor, which we have called EP-activating factor (EPAF), plays a significant role in the development of fever in states of delayed hypersensitivity in man.

Concanavalin A↗
PubMed1997

The superantigen streptococcal pyrogenic exotoxin C (SPE-C) exhibits a novel mode of action.

Recombinant streptococcal pyrogenic exotoxin C (SPE-C) is a potent superantigen that stimulates Vbeta2-bearing human T cells, but is inactive in mice. SPE-C binds with high affinity to both human HLA-DR and murine I-E molecules, but not to murine I-A molecules in a zinc-dependent fashion. Competition binding studies with other recombinant toxins revealed that SPE-C lacks the generic low affinity major histocompatibility complex (MHC) class II alpha-chain binding site common to all other bacterial superantigens. Despite this, SPE-C cross-links MHC class II to induce homotypic aggregation of class II-bearing B cells. Nondenaturing sodium dodecyl sulfate electrophoresis and size exclusion chromatography revealed that both wild-type and recombinant SPE-C exist in a stable dimer at neutral or alkaline pH. These data support a recent crystal structure of SPE-C and reveal yet another mechanism by which bacterial superantigens ligate and cross-link MHC class II.

Bacterial Proteins↗
PubMed1998

Plasmodium falciparum produces prostaglandins that are pyrogenic, somnogenic, and immunosuppressive substances in humans.

Plasmodium falciparum causes the most severe form of human malaria, which kills approximately 1.5-2.7 million people every year, but the molecular mechanisms underlying the clinical symptoms and the host-parasite interaction remain unclear. We show here that P. falciparum produces prostaglandins (PGs) D2, E2, and F2alpha. After incubation with 1 mM arachidonic acid (AA), cell homogenates of P. falciparum produced PGs as determined by enzyme immunoassay and gas chromatography-selected ion monitoring. PG production in the parasite homogenate was not affected by the nonsteroidal antiinflammatory drugs aspirin and indomethacin, and was partially heat resistant, whereas PG biosynthesis by mammalian cyclooxygenase was completely inhibited by these chemicals and by heat treatment. Addition of AA to the parasite cell culture markedly increased an ability of the parasite cell homogenate to produce PGs and of parasitized red blood cells to accumulate PGs in the culture medium. PGD2 and PGE2 accumulated in the culture medium at the stages of trophozoites and schizonts more actively than at the ring stage. These findings are the first evidence of the direct involvement of a malaria parasite in the generation of substances that are pyrogenic and injurious to the host defenses. We will discuss a possible contribution of the parasite-produced PGs to pathogenesis and host-parasite interaction of P. falciparum.

Animals↗
PubMed1988

Vasopressor responses and hyperthermia by intracerebroventricular injections of penicillin, a pyrogen, in rats: involvement of brain angiotensin II.

Because hypothalamus is a center for both the blood pressure and thermoregulation, we assumed that there is a close interrelationship between them. To prove this hypothesis, effects of intracerebroventricular (ICV) injections of a pyrogen, penicillin-G (Pc), on the blood pressure and rectal temperature (RT) were investigated. The ICV injections increased the mean arterial pressure (MAP), heart rate (HR) and the abdominal sympathetic activity (SNA) dose-dependently in urethane-anesthetized rats. In conscious rats, Pc (100 U) elicited the two components of rises in MAP (+19 +/- 1 and +20 +/- 1 mm Hg), and both the RT and HR increased corresponding to the second phase of MAP responses (+1.0 +/- 0.1 degree C and +60 +/- 7 beats/min). ICV injections of an angiotensin II (ang II) antagonist significantly decreased the MAP (-30 +/- 4 mm Hg), HR (-106 +/- 13 beats/min), and the RT (-0.9 +/- 0.1 degree C). ICV injections of Pc elicited drinking behavior (the vehicle group; 1.1 ml/90 min vs Pc group; 8.6 ml) in rats water-deprivated for 24 hours. In spontaneously hypertensive rats (SHRs), ICV injections of Pc elicited augmented responses in the first phase but diminished in the second pressor phase. ICV injections of an ang II antagonist elicited augmented effects in both the MAP (-39 +/- 1 mm Hg) and RT (-0.8 +/- 0.1 degree C) in SHRs. Thus, RT fluctuated corresponding to the blood pressure level in the latter phase, where a brain ang II mechanism may be involved.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II↗
PubMed1999

Structural basis for the recognition of superantigen streptococcal pyrogenic exotoxin A (SpeA1) by MHC class II molecules and T-cell receptors.

Streptococcal pyrogenic exotoxin A (SpeA) is a superantigen produced by Streptococcus pyogenes and is associated with severe infections characterized by rash, hypotension, multiorgan failure and a high mortality rate. In this study, an allelic form of this toxin, SpeA1, was crystallized with four molecules in the crystallographic asymmetric unit and its crystal structure was determined at 2.6 A resolution. The crystallographic R-factor was 19.4% (33 497 reflections) for 7031 protein atoms and 88 water molecules. The overall structure of SpeA1 is considerably similar to that of other prototype microbial superantigens, either of staphylococcal or streptococcal origin, but has greatest similarity to staphylococcal enterotoxin C (SEC). Based on structural and mutagenesis data, we have mapped several important residues on the toxin molecule, which are involved in the recognition of major histocompatibility complex (MHC) class II molecules and T-cell receptors. Also, the toxin appears to possess a potential zinc-binding site which may have implications in binding to particular MHC class II molecules. Finally, we propose models for SpeA1-MHC class II and SpeA1-T-cell receptor association and the relevance of this phenomenon to the superantigenic action of this toxin is considered.

Amino Acid Sequence↗
PubMed1981

Production of leukocytic pyrogen from phagocytes of neonates.

To study the lack of fever during the human newborn period, cord blood leukocytes obtained at birth were stimulated to produce leukocytic pyrogen (LP) in vitro. Phagocytic leukocytes from infants who were born by Caesarean section and whose mothers had not experienced natural onset of labor produced no LP or significantly less LP than leukocytes from adults or from infants born after natural onset of labor. There was a significant difference between total white blood cell count in cord blood of infants whose phagocytic cells produced LP and those whose cells did not. This observation could not be accounted for by anesthetic agents, phagocytosis of staphylococci, or number of leukocytes producing LP; thus, they suggest an intrinsic defect in the ability to produce LP before birth. Of interest is that a nondialyzable substance(s) present in crude preparations of human chorionic gonadotropin markedly suppressed LP production from adult human monocytes, but purified human chorionic gonadotropin had no effect.

Blood Proteins↗
PubMed1991

Stability of streptococcal pyrogenic exotoxin production with laboratory manipulation of group A streptococci.

Because of reported differences in the production of streptococcal pyrogenic exotoxins by group A strains associated with severe streptococcal infections, the stability of exotoxin production by specific strains was examined by passing group A streptococci on blood agar culture plates daily for 20 days. No changes were detected in either exotoxin genes or in exotoxin production during this time, suggesting that these reported differences are due to other explanations such as differences in the strains collected from various geographic areas or to laboratory methodologic differences.

Bacterial Proteins↗
PubMed1992

Streptococcal toxic shock syndrome: synthesis of tumor necrosis factor and interleukin-1 by monocytes stimulated with pyrogenic exotoxin A and streptolysin O.

Previous studies have found that 80% of strains isolated from patients with the streptococcal toxic shock syndrome produce pyrogenic exotoxin A (SPEA) and 100% produced streptolysin O (SLO). To elucidate the cellular mechanisms contributing to shock, human monocytes were stimulated with SPEA (0.1-10 micrograms/10(6) monocytes) or SLO (0.2-2.5 hemolytic units/10(6) monocytes), and production of tumor necrosis factor (TNF)-alpha and interleukin (IL)-1 beta was measured at 24, 48, and 72 h. SPEA and SLO were potent inducers of TNF alpha, with maximum production occurring at 72 h for SPEA and at 48 h for SLO (1067 and 687 pg/ml, respectively). In contrast, IL-1 beta production was greater for SLO than for SPEA (557 vs. 258 pg/ml). In addition, the effects of SPEA and SLO together were synergistic in terms of monocyte IL-1 beta production: SPEA, 193 pg/ml; SLO, 452 pg/ml; SPEA plus SLO, 799 pg/ml. These findings suggest TNF alpha and IL-1 beta are important candidates for mediating shock in severe streptococcal infections.

Bacterial Proteins↗
PubMed1992

Streptococcal pyrogenic exotoxin A and streptolysin O enhance polymorphonuclear leukocyte binding to gelatin matrixes.

Autopsy data from cases of streptococcal toxic shock demonstrate accumulation of polymorphonuclear leukocytes (PMNL) within lung and soft tissue microvasculature. Because of the increased prevalence of streptococcal pyrogenic exotoxin A (SPEA)-producing strains associated with streptococcal toxic shock syndrome, experiments were done to determine whether SPEA or streptolysin O (SLO, a thiol-activated cytolysin produced by all group A streptococci) could stimulate PMNL-dependent adherence mechanisms in vitro. SPEA (0.01-10 micrograms/5.5 x 10(6) PMNL) only modestly enhanced PMNL adherence over the entire range of concentrations tested. In contrast, SLO-induced PMNL binding was highly dose dependent (maximal binding, 55.1 +/- 1.6% at 0.5 hemolytic units/5.5 x 10(6) PMNL) and was mediated by CD11/CD18 adherence glycoprotein.

Antigens, CD↗
PubMedDate not supplied

Pyrogen retention by the Asahi APS-650 polysulfone dialyzer during in vitro dialysis with whole human donor blood.

The purpose of this study was to test the pyrogen permeability of the new Asahi polysulfone APS 650 (APS) dialyzer membrane with a high permeability for middle molecules (up to 40 kDa) in comparison with the high-flux Fresenius polysulfone F60S (F60S) membrane. Dialyzers were tested in parallel in vitro dialysis experiments with whole human donor blood in the blood compartment and contaminated bicarbonate dialysate in the dialysate compartment. Dialysate was contaminated by a filtrate (0.45 microm) of a Pseudomonas aeruginosa culture in bicarbonate dialysate. The production of interleukin-1beta (IL-1beta) and tumor necrosis factor alpha (TNFalpha) in whole blood samples taken from the in vitro dialysis system was used to detect the passage of cytokine inducing bacterial substances derived from P. aeruginosa across the two highflux polysulfone membranes. Compared with a sterile control period at the beginning of each experiment (n = 5), the TNFalpha inducing activity in the dialysate increased from (mean +/- SEM) 42 +/- 12 pg/ml to 1,288 +/- 356 pg/ml with F60S dialyzers and from 37 +/- 10 pg/ml to 928 +/- 249 pg/ml with APS dialyzers 30 minutes after the dialysate was contaminated. The IL-1beta inducing activity in the dialysate increased similarly. In the presence of this significant contamination in the dialysate, whole blood circulating in the blood compartments for 60 minutes was not stimulated to produce increased amounts of TNFalpha or IL-1beta with neither of the two tested membranes. We conclude that F60S and APS membranes are equal in their ability to prevent the passage of cytokine inducing bacterial substances from highly contaminated dialysate into the patients' blood during hemodialysis.

Blood Donors↗
PubMed1993

Biological activities of cell envelope fragments of the archaeobacterium Sulfolobus solfataricus: lethal toxicity, local hypersensitivity, pyrogenicity and spleen lymphocyte mitogenicity.

The sensitizing effect and the local and general toxicity related to membrane components of the archaeobacterium Sulfolobus solfataricus was studied. Cell envelope fragments were biologically active but this activity was lost upon separation of the lipid and protein components. The envelope fragments exerted lethal effects on mice sensitized with D-galactosamine that were prevented by pretreatment with anti-TNF-alpha serum. This lethal activity occurred in both LPS-responder (BALB/cByJ) and LPS-nonresponder (C3H/HeJ) mouse strains. In addition, Sulfolobus envelope fragments tested in rabbits caused a local Schwartzman reaction, and showed pyrogenic activity. In vitro, the envelope fragments that act on spleen lymphocytes of the LPS-responder (BALB/cByJ) and LPS-nonresponder (C3H/HeJ) mice caused an uptake of [3H]thymidine similar to that caused by concanavalin A. A similar toxic activity to that exerted by eubacteria is therefore exerted by this non-pathogenic archaeobacterium despite the difference in surface chemistry.

Animals↗