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Clinical Microbiology Reviews Jul 1995The recent discovery of the mode of interaction between a group of microbial proteins known as superantigens and the immune system has opened a wide area of... (Review)
Review
The recent discovery of the mode of interaction between a group of microbial proteins known as superantigens and the immune system has opened a wide area of investigation into the possible role of these molecules in human diseases. Superantigens produced by certain viruses and bacteria, including Mycoplasma species, are either secreted or membrane-bound proteins. A unique feature of these proteins is that they can interact simultaneously with distinct receptors on different types of cells, resulting in enhanced cell-cell interaction and triggering a series of biochemical reactions that can lead to excessive cell proliferation and the release of inflammatory cytokines. However, although superantigens share many features, they can have very different biological effects that are potentiated by host genetic and environmental factors. This review focuses on a group of secreted pyrogenic toxins that belong to the superantigen family and highlights some of their structural-functional features and their roles in diseases such as toxic shock and autoimmunity. Deciphering the biological activities of the various superantigens and understanding their role in the pathogenesis of microbial infections and their sequelae will enable us to devise means by which we can intervene with their activity and/or manipulate them to our advantage.
Topics: Autoimmune Diseases; Bacterial Infections; Exotoxins; Humans; Pyrogens; Superantigens; T-Lymphocytes
PubMed: 7553574
DOI: 10.1128/CMR.8.3.411 -
American Journal of Obstetrics and... Jan 2014The purpose of this study was to evaluate the quality of compounded 17-hydroxyprogesterone caproate (17-OHPC).
OBJECTIVE
The purpose of this study was to evaluate the quality of compounded 17-hydroxyprogesterone caproate (17-OHPC).
STUDY DESIGN
Compounded 17-OHPC that was obtained from 15 compounding pharmacies throughout the United States was analyzed for potency, impurities, sterility, and pyrogen status.
RESULTS
Eighteen samples were supplied by 15 compounding pharmacies. The concentration of 17-OHPC in all samples was within the specification limits, and all tested samples passed sterility and pyrogen testing. Only 1 of 18 samples was out of specification limits for impurities.
CONCLUSION
Compounded 17-OHPC that was obtained from 15 pharmacies throughout the United States did not raise safety concerns when assessed for potency, sterility, pyrogen status, or impurities.
Topics: 17 alpha-Hydroxyprogesterone Caproate; Drug Compounding; Humans; Hydroxyprogesterones; Pyrogens; Quality Assurance, Health Care; Quality Control; United States
PubMed: 24200163
DOI: 10.1016/j.ajog.2013.09.039 -
The Journal of Experimental Medicine May 1978Tumor-associated fever occurs commonly in acute leukemias and lymphomas. We investigated the capacity for in vitro production of pyrogen by three mouse histiocytic...
Tumor-associated fever occurs commonly in acute leukemias and lymphomas. We investigated the capacity for in vitro production of pyrogen by three mouse histiocytic lymphoma cell lines (J-774, PU5-1.8, p 388 D1), one myelomonoyctic line (WEHI-3), and tow lymphoma-derived lines, RAW-8 and R-8. Pyrogen was released spontaneously into the culture medium during growth by all cell lines with macrophage or myeloid characteristics including lysozyme production; R-8 cells, of presumed B-lymphocyte origin, did not produce pyrogen. When injected into mice, the pyrogens gave fever curves typical of endogenous pyrogen, were inactived by heating to 56 degrees C and by pronase digestion, and appeared to be secreted continuously by viable cells. Two pyrogenic molecular species produced by H-774 cells were identified by Sephadex filtration, one of mol wt approximately equal to 30,000, and the other greater than or equal to 60,000. By contrast, three carcinoma cell lines of human origin and SV-40 3T3 mouse fibroblasts did not produce pyrogen in vitro. These results suggest that some malignant cells derived from phagocytic cells of bone marrow origin retain their capacity for pyrogen production, and may spontaneously secrete pyrogen during growth.
Topics: Adenocarcinoma; Animals; B-Lymphocytes; Cell Line; Cells, Cultured; Histiocytes; Humans; Leukemia, Experimental; Leukemia, Myeloid; Lymphoma; Macrophages; Mice; Pyrogens
PubMed: 306417
DOI: No ID Found -
Microorganisms Jun 2021Generalised modules for membrane antigens (GMMA)-based vaccines comprise the outer membrane from genetically modified Gram-negative bacteria containing membrane...
Generalised modules for membrane antigens (GMMA)-based vaccines comprise the outer membrane from genetically modified Gram-negative bacteria containing membrane proteins, phospholipids and lipopolysaccharides. Some lipoproteins and lipopolysaccharides are pyrogens; thus, GMMA-based vaccines are intrinsically pyrogenic. It is important to control the pyrogenic content of biological medicines, including vaccines, to prevent adverse reactions such as febrile responses. The rabbit pyrogen test (RPT) and bacterial endotoxin test (BET) are the most commonly employed safety assays used to detect pyrogens. However, both tests are tailored for detecting pyrogenic contaminants and have considerable limitations when measuring the pyrogen content of inherently pyrogenic products. We report the adaptation of the monocyte activation test (MAT) as an alternative to the RPT for monitoring the pyrogenicity of GMMA-based vaccines. The European Pharmacopoeia endorses three MAT methods (A-C). Of these, method C, the reference lot comparison test, was identified as the most suitable. This method was evaluated with different reference materials to ensure parallelism and consistency for a mono- and multi-component GMMA vaccine. We demonstrate the drug substance as a promising reference material for safety testing of the matched drug product. Our results support the implementation of MAT as an alternative to the RPT and use of the defined parameters can be extended to GMMA-based vaccines currently in development, aiding vaccine batch release.
PubMed: 34202832
DOI: 10.3390/microorganisms9071375 -
Annals of Occupational and... 2022Haenyeo is a woman who has the job of collecting seafood in the Jeju Sea at an average temperature of 13°C-14°C. The purpose of this study was to examine the cold...
BACKGROUND
Haenyeo is a woman who has the job of collecting seafood in the Jeju Sea at an average temperature of 13°C-14°C. The purpose of this study was to examine the cold acclimatization and occupational characteristics of Haenyeo through biomarkers such as orexin and irisin related to heat generation in the body.
METHODS
Twenty-one Haenyeo and 25 people with similar age, body type, and body mass index were selected as the control group (Control G). In the cold exposure experiment, a climate chamber was set to 5°C and both feet were immersed in a 15°C water tank for 30 minutes. Tympanic temperature (T) and skin temperature (T) were measured, and the mean body temperature (mT) was calculated. Blood samples were collected before and immediately after the examination. Orexin and irisin levels were analyzed.
RESULTS
Orexin levels were elevated after cold stimulation from 12.17 ± 4.44 to 12.95 ± 4.53 ng/mL (Haenyeo group [Haenyeo G], < 0.01) and 10.37 ± 3.84 to 11.25 ± 4.02 ng/mL (Control G, < 0.001). Irisin levels were elevated after cold stimulation from 4.83 ± 2.28 to 5.36 ± 2.23 ng/mL (Haenyeo G, < 0.001) and 3.73 ± 1.59 to 4.18 ± 2.04 ng/mL (Control G, < 0.001). The difference between Haenyeo G and Control G values in orexin and irisin appears not only in pre-exposure but also in post-exposure ( < 0.05).
CONCLUSIONS
Our experimental results suggest that Haenyeo G were relatively superior in cold tolerance to Control G under cold exposure conditions. Haenyeo's cold acclimatization is due to the basic differences in pyrogens regarding body temperature control such as orexin and irisin. This means that Haenyeo are advantageous for cold survival.
PubMed: 36452252
DOI: 10.35371/aoem.2022.34.e28 -
European Journal of Biochemistry Apr 1985The recently chemically synthesized Escherichia coli lipid A and the natural free lipid A of E. coli were compared with respect to their endotoxic activities in the... (Comparative Study)
Comparative Study
The recently chemically synthesized Escherichia coli lipid A and the natural free lipid A of E. coli were compared with respect to their endotoxic activities in the following test systems: lethal toxicity, pyrogenicity, local Shwartzman reactivity, Limulus amoebocyte lysate gelation capacity, tumour necrotizing activity, B cell mitogenicity, induction of prostaglandin synthesis in macrophages, and antigenic specificity. It was found that synthetic and natural free lipid A exhibit identical activities and are indistinguishable in all tests.
Topics: Animals; Cell Survival; Drug Tolerance; Endotoxins; Epitopes; Escherichia coli; In Vitro Techniques; Lethal Dose 50; Limulus Test; Lipid A; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mitogens; Necrosis; Prostaglandins; Pyrogens; Rabbits; Sarcoma, Experimental; Shwartzman Phenomenon
PubMed: 2579812
DOI: 10.1111/j.1432-1033.1985.tb08798.x -
Journal of Clinical Microbiology Nov 1999Streptococcal pyrogenic exotoxin A (SPE-A) and SPE-B have been implicated in the pathogenesis of severe group A streptococcal (GAS) disease. We studied 31 invasive GAS...
Streptococcal pyrogenic exotoxin A (SPE-A) and SPE-B have been implicated in the pathogenesis of severe group A streptococcal (GAS) disease. We studied 31 invasive GAS strains including 18 isolates from patients with toxic shock syndrome and 22 noninvasive strains isolated in The Netherlands between 1994 and 1998. These strains were associated with the different allelic variants of the gene encoding SPE-A. We selected endemic strains with speA-positive M and T serotypes: speA2-associated M1T1 and M22-60T12 strains, speA3-associated M3T3 strains, and speA4-associated M6T6 strains. Since speA1-positive isolates were not frequently encountered, we included speA1 strains of different serotypes. The GAS strains were compared genotypically by pulsed-field gel electrophoresis and phenotypically by the in vitro production of SPE-A and SPE-B. All strains within one M and T type appeared to be of clonal origin. Most strains produced SPE-A and SPE-B, but only a minority of the speA4-positive isolates did so. Among our isolates, speA1- and speA3-positive strains produced significantly more SPE-A than speA2- and speA4-carrying strains, while SPE-B production was most pronounced among speA1- and speA2-containing strains. There was a marked degree of variability in the amounts of exotoxins produced in vitro by strains that shared the same genetic profile. We conclude that the differences in the in vitro production of SPE-A and SPE-B between our selected strains with identical M and T types were not related to either genetic heterogeneity or the clinical course of GAS disease in the patient from whom they were isolated.
Topics: Alleles; Bacterial Proteins; Bacterial Typing Techniques; Base Sequence; Electrophoresis, Gel, Pulsed-Field; Exotoxins; Genes, Bacterial; Genetic Variation; Humans; Membrane Proteins; Netherlands; Oligonucleotide Probes; Pyrogens; Serotyping; Shock, Septic; Streptococcal Infections; Streptococcus pyogenes
PubMed: 10523536
DOI: 10.1128/JCM.37.11.3469-3474.1999 -
Transactions of the American Clinical... 1975Certain of the mechanisms by which man develops pyrogenic tolerance to bacterial endotoxins have been considered. After an initial intravenous injection of toxin, two...
Certain of the mechanisms by which man develops pyrogenic tolerance to bacterial endotoxins have been considered. After an initial intravenous injection of toxin, two temporally distinct phases of tolerance can be discerned, early and late, each with very different characteristics. Early tolerance appears to be mediated by a non-antibody mechanism entailing a transiently occurring refractory state, apparently involving to a major degree decreased production of endogenous pyrogen by the macrophage system, particularly the hepatic macrophages. Late tolerance appears to be mediated by anti-endotoxin antibodies directed against both "O" and common core antigens which blunt the release of endogenous pyrogen from macrophages. The common core antigens are masked in the presence of the "O" antigenic side chains and become effective immunogens only when these "O" side chains are lacking. Accelerated reticuloendothelial system clearance of circulating endotoxin provides an ancillary protective mechanism in that it brings the toxin more efficiently into the macrophages that are refractory or protected by antibody. When endotoxin is administered repeatedly at closely spaced intervals, both the early phase (non-immune) and late phase (immune) mechanisms may become superimposed. In addition, a third mechanisms, enhanced detoxification capabilities of macrophages, also now appears to come into play. At any given time, it is the relative contribution of each mechanism, which in turn is dependent upon the immunization schedule, antigenicity of the endotoxin, dosage, and immunological competency of the host, that determines the expression of the endotoxin tolerant state.
Topics: Antibody Formation; Drug Tolerance; Endotoxins; Humans; Immune Tolerance; Liver; Macrophages; Pyrogens; Time Factors
PubMed: 1179593
DOI: No ID Found -
The Journal of Physiology Nov 19791. Experiments were conducted to localize the hypothalamic site of action of microinjected leucocytic pyrogen and to compare the pyrogenic sensitivity of this locus in...
1. Experiments were conducted to localize the hypothalamic site of action of microinjected leucocytic pyrogen and to compare the pyrogenic sensitivity of this locus in adult and new-born guinea-pigs.2. To identify the site reactive to leucocytic pyrogen, bilateral (0.8-1.0 mm from the mid line) injections of 1 microliter were made into conscious adult guinea-pigs via cannulas stereotaxically palced at 0.5 mm intervals and varying depths from the olfactory tegmentum to the mammillary bodies. Injections into the preoptic area produced sharp monophasic fevers with short latencies, whereas injections into circumjacent sites evoked smaller fevers with longer latencies. 3. To assess the ontogeny of the pyrogenic sensitivity of this locus, the febrile response to 1.00, 0.50, and 0.25 microliter leucocytic pyrogen injected bilaterally was compared to 0 to 5-, 6 to 12-, and 13 to 16-day old and in adult guinea-pigs. The minimum pyrogenic dose in both new-born and adult guinea-pigs was 0.25 microliter, but the 0 to 5-day old animals which responded with a fever to this dose were few in number and large in weight; 'small-for age' neonates became hypothermic. 4. The number of febrile animals increased with age; it also could be increased by increasing the dose of leucocytic pyrogen at any age. 5. These results suggest that febrile responsiveness may depend on the stage of development of, presumably, the pyrogen-receptive mechanism. They further imply that the preoptic sites where leucocytic pyrogen acts and thermoafferents are integrated may not be the same, since thermoregulatory capability is fully competent from birth.
Topics: Aging; Animals; Animals, Newborn; Body Temperature; Dose-Response Relationship, Drug; Female; Guinea Pigs; Hypothalamus; Leukocytes; Male; Preoptic Area; Pyrogens
PubMed: 529081
DOI: 10.1113/jphysiol.1979.sp012998 -
Infection and Immunity Dec 1983Many of the metabolic sequelae to infection and inflammation, such as fever, trace mineral redistribution, skeletal muscle catabolism, and the acute-phase protein... (Comparative Study)
Comparative Study
Many of the metabolic sequelae to infection and inflammation, such as fever, trace mineral redistribution, skeletal muscle catabolism, and the acute-phase protein response, are mediated by leukocytic pyrogen (interleukin 1). In the anterior hypothalamus and in skeletal muscles leukocytic pyrogen appears to induce the synthesis of prostaglandin E2 which mediates fever and skeletal protein catabolism. It is unclear whether any additional metabolic responses to leukocytic pyrogen result from prostaglandin production. This study was undertaken to investigate the ability of ibuprofen, a specific cyclooxygenase inhibitor, to alter protein and trace metal responses to leukocytic pyrogen or endotoxin when given in quantities sufficient to block the febrile response. In guinea pigs given continuous infusions of leukocytic pyrogen or endotoxin, a 0.6 to 0.8 degrees C fever was observed within 4 h, and zinc and iron concentrations in serum fell by 63 to 78% (P less than 0.01). Rates of whole body amino acid appearance, oxidation, and incorporation into protein were all significantly increased by leukocytic pyrogen and endotoxin treatment, (P less than 0.05) as were the fractional hepatic and seromucoid protein synthesis rates in leukocytic pyrogen-treated animals (P less than 0.01). Muscle protein synthesis was unchanged. Although pretreatment with infusions of ibuprofen completely ablated the febrile response to leukocytic pyrogen and endotoxin, decreases in zinc and iron concentrations in serum and leukocytosis were unaffected. Overall increases in whole body amino acid kinetics induced by leukocytic pyrogen or endotoxin were only minimally affected by ibuprofen. We concluded that treatment with prostaglandin synthesis inhibitor ibuprofen did not affect whole body trace metal, hematological, or hepatic acute-phase-induced responses to leukocytic pyrogen or endotoxin, either because these responses are prostanoid independent or because they are only partially mediated by eicosanoid products.
Topics: Animals; Drug Evaluation, Preclinical; Endotoxins; Fever; Guinea Pigs; Humans; Ibuprofen; Interleukin-1; Leukocytes; Male; Pyrogens; Salmonella enteritidis; Time Factors
PubMed: 6358043
DOI: 10.1128/iai.42.3.997-1005.1983