Biology of Endotoxin

Elin, Ronald J.; Wolff, SheldonM.

doi:10.1146/annurev.me.27.020176.001015

Cited by 134 publications

(49 citation statements)

References 74 publications

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“…Interferon-preparations were at most marginally pyrogenic in rabbits. The febrile reactions were not accompanied by granulocytosis, and none of the patients developed hyporeactivity, both constant features ofendotoxin reactions in humans (13,28).…”

Section: Serum Titers Of Interferon In Humansmentioning

confidence: 99%

Human Fibroblast Interferon for Clinical Trials: Pharmacokinetics and Tolerability in Experimental Animals and Humans

Billiau

Somer

Edy

et al. 1979

Antimicrob Agents Chemother

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Human fibroblast interferon (F-interferon) purified by adsorption on controlled-pore glass was given intramuscularly to patients at daily dosages of up to 20 x 106 units. Serum levels of antiviral activity were low or undetectable. In contrast, reasonably high serum titers were found in patients receiving interferon prepared from leukocytes (L-interferon). Similarly, in rabbits lower serum titers were seen with F-interferon than with L-interferon. These results are at variance with those obtained earlier

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Section: Serum Titers Of Interferon In Humansmentioning

confidence: 99%

Human Fibroblast Interferon for Clinical Trials: Pharmacokinetics and Tolerability in Experimental Animals and Humans

Billiau

Somer

Edy

et al. 1979

Antimicrob Agents Chemother

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“…LPS imitates a bacterial infection and triggers an inflammatory response and all its associated costs in terms of energy and nutrients. However, LPS itself does not actually cause any sickness; thus, any changes in physiology are purely the result of the immune response (Elin and Wolff, 1976). Hence, by using a LPS inoculation we would be able to identify differences in inflammatory response between the HR and C lines.…”

Section: Introductionmentioning

confidence: 99%

Within-lifetime trade-offs but evolutionary freedom for hormonal and immunological traits: evidence from mice bred for high voluntary exercise

Downs

Schutz

Meek

et al. 2012

Journal of Experimental Biology

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SUMMARYChronic increases in circulating corticosterone (CORT) generally suppress immune function, but it is not known whether evolved increases necessarily have similar adverse effects. Moreover, the evolution of immune function might be constrained by the sharing of signaling molecules, such as CORT, across numerous physiological systems. Laboratory house mice (Mus domesticus Linnaeus) from four replicate lines selectively bred for high voluntary wheel running (HR lines) generally had baseline circulating CORT approximately twofold higher than in four non-selected control (C) lines. To test whether elevated baseline CORT suppresses the inflammatory response in HR mice, we injected females with lipopolysaccharide (LPS). All mice injected with LPS exhibited classic signs of an inflammatory response, including sickness behavior, loss of body mass, reduced locomotor activity (i.e. voluntary wheel running), enlarged spleens and livers, elevated hematocrit and elevated inflammatory cytokines. However, as compared with C mice, the inflammatory response was not suppressed in HR mice. Our results, and those of a previous study, suggest that selective breeding for high voluntary exercise has not altered immune function. They also suggest that the effects of evolved differences in baseline CORT levels may differ greatly from effects of environmental factors (often viewed as ʻstressorsʼ) that alter baseline CORT during an individualʼs lifetime. In particular, evolved increases in circulating levels of ʻstress hormonesʼ are not necessarily associated with detrimental suppression of the inflammatory response, presumably as a result of correlated evolution of other physiological systems (counter-measures). Our results have important implications for the interpretation of elevated stress hormones and of immune indicators in natural populations. Supplementary material available online at

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“…Bacterial endotoxins are known to possess a variety of biological effects in vivo (1). Some of these, such as activation ofthe complement and coagulation cascades, represent, in part, direct effects of lipopolysaccharides (LPS)l on target cells (leukocytes, platelets, macrophages), possibly via adsorption to membrane receptors (2)(3)(4), whereas other hemodynamic -and metabolic consequences of endotoxemia are presumed to be largely mediated by subsequent increased blood levels of proteolytic enzymes or vasoactive substances of lysosomal and extralysosomal origin (5)(6)(7).…”

Section: Introductionmentioning

confidence: 99%

Some Effects of the Administration of Endotoxin in Mice

Gorevic¹,

Levo²,

Chatpar³

et al. 1979

J. Clin. Invest.

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A B S T R A C T Endotoxin has been shown to induce amyloidosis in mice and to result in the appearance in serum of large amounts of amyloidrelated protein (SAA). After injection of 300 j.g lipopolysaccharide Escherichia coli, SAA behaves as an acute phase reactant with levels reaching a peak of >600 Ag/ml at 18-22 h and returning to base line (<50 ,ug/ml) by 48 h in each of four strains tested; only the endotoxin-resistant C3H/HeJ strain showed a smaller response. Lesser, though significant, elevations were also found after subcutaneous injection of 25 mg of casein, bovine serum albumin, ovalbumin, or monomeric immunoglobulin G, whereas pyrogen-free human serum albumin/U. S. Pharmacopeia failed to raise SAA levels. SAA generation may thus be a result of endotoxin contamination of these protein preparations.Also present in equivalent amounts in acidified serum from endotoxin-treated mice, but barely detectable in control sera, was a 3,000-dalton molecule whose amino acid sequence is identical to the amino terminal 24 residues of mouse albumin. The appearance of SAA and the atnino terminal albumin fragment after endotoxin were unaffected by pretreatment with cobra venom factor, and equivalent levels were found in CS-deficient mice. Pretreatment with pepstatin in vivo, or before acidification in vitro, prevented the appearance of the albumin fragment but had no effect on the appearance of SAA, whereas leupeptin and antipain did not affect the appearance of either SAA or the albumin fragment. These studies suggest that the generation of SAA after endotoxin administration does not involve complement activation or intravascular proteolytic activity, whereas the liberation of a specific peptic-like cleavage product of albumin appears to be the consequence of an acid protease.

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Biology of Endotoxin

Cited by 134 publications

References 74 publications

Human Fibroblast Interferon for Clinical Trials: Pharmacokinetics and Tolerability in Experimental Animals and Humans

Human Fibroblast Interferon for Clinical Trials: Pharmacokinetics and Tolerability in Experimental Animals and Humans

Within-lifetime trade-offs but evolutionary freedom for hormonal and immunological traits: evidence from mice bred for high voluntary exercise

Some Effects of the Administration of Endotoxin in Mice

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