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[The effects and properties of sodium nucleinate as a pyrogen working standard. 6. Pyrogen inactivation by incubation with blood serum or blood plasma].

The 24-h storage of horse serum at 4 degrees C to which bacterial lipopolysaccharide (P) or sodium nucleinate (NN) was added, did not change the pyrogenic effect of these mixtures. Even after 2-h incubation at 37 degrees C changes could not be clearly detected. 24-h incubation at 37 degrees C leads to a clear, but only in case of NN, statistically significant reduction of pyrogenic effect. 24-h incubation of human heparin plasma at 37 degrees C, to which P or NN was added, in both cases resulted in statistically significant reductions of pyrogenic effect. Thus, when incubated with horse serum or human heparin plasma, the pyrogenic effect of NN is reduced in principle as well as that of P treated in the same way.

Animals↗

Ultrasonication of pyrogenic microorganisms improves the detection of pyrogens in the Mono Mac 6 assay.

The monocytic cell line Mono Mac 6 is sensitive to pyrogens. When exposed to pyrogens secretion of interleukin-6 is induced. However, some eukaryotic pyrogenic microorganisms are not detectable. The aim of this study is to introduce a pretreatment of samples to expand the detection range of the assay. The interleukin-6 inducing capacity of a broad spectrum of UV-killed and ultrasonicated microorganisms is examined in Mono Mac 6 cells. The interleukin-6 secretion is determined in a sandwich immunoassay (DELFIA). The Mono Mac 6 assay is able to detect UV-killed Bacillus subtilis, Staphylococcus aureus and Salmonella typhimurium, but neither Candida albicans nor Aspergillus niger. After ultrasonication of the microorganisms it is possible to detect C. albicans and A. niger. The interleukin-6 inducing ability of the examined microorganisms is in no case reduced after ultrasonic treatment. However, ultrasonication of S. aureus results in a 100-fold increase in the interleukin-6 response. Even after ultrasonication Streptococcus faecalis can not be detected. Ultrasonication is an easy and simple method for expanding the detection range in the Mono Mac 6 assay.

Candida albicans↗

Reliability of the rabbit pyrogen test and of the limulus test in predicting the pyrogenicity of vaccines in man.

Commercial vaccines including bacterial as well as live and inactivated viral vaccines were examined in the rabbit pyrogen test and in the limulus test. The laboratory results were compared with the reactivity in humans. A fairly good correlation was found between the temperature rise in rabbits and the frequency of febrile reaction in the vaccinees. Two rabies vaccines and a tick-borne encephalitis virus vaccine, each pyrogenic both in rabbit and in man. were negative in the limulus test. The pyrogenicity of these vaccines is attributed to the vaccine virus itself.

Bacterial Vaccines↗

Pyrogenicity and cytokine-inducing properties of Streptococcus pyogenes superantigens: comparative study of streptococcal mitogenic exotoxin Z and pyrogenic exotoxin A.

Streptococcal mitogenic exotoxin Z (SMEZ), a superantigen derived from Streptococcus pyogenes, provoked expansion of human lymphocytes expressing the Vbeta 2, 4, 7 and 8 motifs of T-cell receptor. SMEZ was pyrogenic in rabbits and stimulated the expression of the T-cell activation markers CD69 and cutaneous lymphocyte-associated antigen. A variety of cytokines was released by human mononuclear leukocytes stimulated with SMEZ, which was 10-fold more active than streptococcal pyrogenic exotoxin A. Th2-derived cytokines were elicited only by superantigens and not by streptococcal cells.

Animals↗

Comparison of endotoxin and leukocytic pyrogen pyrogenicity in newborn guinea pigs.

Guinea pigs under 8 days of age generally are unable to develop fever (viz., deltaTre greater than 0.5 degrees C) in response to a standardized dose of endotoxin (2 mug/kg iv of Salmonella enteritidis [SE]). This study was undertaken to determine whether this lack of responsiveness might be due to an incapacity of leukocytes from young neonates to produce sufficient leukocytic pyrogen (LP). Three series of experiments were performed at Ta = 27 degrees C: guinea pigs aged 0-2, 4, and 8 days were injected iv with: a) 2, 4, 8, or 16 mug/kg of SE, b) 0.1, 0.5, or 1.0 ml of LP generated by 8 mug of SE/25 X 10(6) leukocytes from adult guinea pigs (LPa), or c) 0.1 or 1.0 ml of LP generated by 8 mug of SE/25 X 10(6) leukocytes from 0-5-, 6-12-, and 13-16-day-old guinea pigs (LPn). Adult guinea pigs received iv 1.0 ml of LPa or LPn. The results revealed that fever could be induced in these animals from birth, but the required doses of SE, LPa and LPn were greater the younger the guinea pigs. Under these conditions, LPn, regardless of the donors' ages, produced fever in all the recipients. It is concluded that the pyrogenic unresponsiveness of newborn guinea pigs to endotoxin may be related not to an inability of leukocytes from these neonates to elaborate LP, but rather to an insensitivity of, presumably, their hypothalamic febrogenic mechanisms to low levels of LP.

Age Factors↗

[The action of pyrogenal and endogenous pyrogen on visceral afferent systems].

Pyrogenal in the dose 5 mcg increased the adrenaline release in dogs. Interleukin-1 increased the noradrenaline release. Neither capsaicin, nor M- and N-cholinoreceptor blockade, nor pre-decentralization of the inferior mesenteric ganglion, abolished the effects. Mechanical and chemical stimuli during continuous perfusion of the colon with subliminal doses of pyrogenal increased the adrenaline release, too. A possible direct effect of endotoxins on peripheral adrenergic neurons, is discussed.

Afferent Pathways↗

Nature of the endogenous pyrogen (EP) induced by influenza viruses: lack of correlation between EP levels and content of the known pyrogenic cytokines, interleukin 1, interleukin 6 and tumour necrosis factor.

Fever in influenza results from the release of endogenous pyrogen (EP) following virus-phagocyte interaction and its level correlates with the differing virulence of virus strains. However, the different levels of fever produced in ferrets by intracardial inoculation of EP obtained from the interaction of different virus strains with ferret of human phagocytes did not correlate with the levels of interleukin 1 (IL-1), IL-6 or tumour necrosis factor in the same samples as assayed by conventional in vitro methods. Hence, the EP produced by influenza virus appears to be different to these cytokines.

Animals↗

[Role of the adenyl cyclase system in achieving the immunogenesis-stimulating action of bacterial lipopolysaccharides--pyrogenal and endogenous serum pyrogen].

Experiments were conducted on rabbits immunized intraperitoneally with corpuscular typhoid vaccine; the number of antibody-forming cells in the spleen proved to increase after tha administration of bacterial lipopolysaccharide (LPS)--pyropeneal, and endogenous serum pyrogen (EPS) together with theopylline. The data obtained indicated that the adenylcyclase system played a certain role in the mechanism of the stimulating action of LPS and EPS.

Adenylyl Cyclases↗