Exogenous Pyrogens

Dinarello, C A; Wolff, Sheldon M.

doi:10.1007/978-3-642-68569-9_4

Cited by 21 publications

(13 citation statements)

References 163 publications

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“…In humans, fever and other constitutional symptoms of influenza (headache, myalgia, listlessness, nausea, shivering, anorexia and depression) result from the action of endogenous pyrogen (EP) produced by phagocytes in response to infection (Rawlins & Cranston, 1973;Scott et al, 1981;Dinarello & Wolff, 1982;Gander, 1982). Influenza viruses vary in their ability to cause these constitutional effects.…”

Section: Introductionmentioning

confidence: 99%

Influenza virus pyrogenicity: central role of structural orientation of virion components and involvement of viral lipid and glycoproteins

Pickering¹,

Smith

Sweet³

1992

Journal of General Virology

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Ultraviolet light-inactivated, non-infectious influenza virus is pyrogenic; virion components are probably responsible for this pyrogenicity. To try to identify the pyrogenic component, influenza virions were disrupted with either bromelain or sodium deoxycholate (DOC). Treatment of infectious virions with bromelain, under conditions that removed the surface glycoproteins (spikes), destroyed their pyrogenicity. The supernatant, containing non-aggregated and modified glycoproteins, was also non-pyrogenic. Disruption ofvirions with DOC considerably reduced pyrogenicity; however, some was retained by the sub-viral cores. Viral nucleoprotein and matrix protein, purified from the supernatant, were non-pyrogenic. Aggregated stellate clusters of surface glycoproteins separated on sucrose gradients were pyrogenic in half of numerous tests performed with different batches of material. Treatment of virus with ether resulted in complete loss of pyrogenicity. Liposomes made from extracted viral lipid were non-pyrogenic. In contrast, virosomes made from the viral lipid and the aggregated stellate clusters of surface glycoproteins were pyrogenic. Hence, optimum pyrogenicity depends upon the integrity of the virus particle, but haemagglutinin and/or neuraminidase appear essential, and lipid may be involved.

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Section: Introductionmentioning

confidence: 99%

Influenza virus pyrogenicity: central role of structural orientation of virion components and involvement of viral lipid and glycoproteins

Pickering¹,

Smith

Sweet³

1992

Journal of General Virology

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“…The existence of IL-1 inhibitor (IL-li) was previously described by Dinarello et al in 1982 which demonstrated the existence of a circulating thymocyte suppressor factor during cndotoxic fever in humans. IL-li biocks the binding of IL-1 to its receptors on Tcells but does not block the binding of TNFcv or 24].…”

Section: Discussionmentioning

confidence: 92%

Human recombinant interleukin‐1 receptor antagonist inhibits lymphocyte blastogenesis induced by concanavalin A Restorative effect of hrIL‐1

Conti

Reale

Panara³

et al. 1991

FEBS Letters

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Interleukin‐1 (IL‐1), mainly produced by monocyte‐macrophages, is a polypeptide cytokine with pleiotropic biological effects. IL‐1 plays an important role in mediating immune response and inflammation. Recently a natural inhibitor to IL‐1 has been discovered, interleukin‐1 receptor antagonist (IL‐1ra), produced by human monocytes cultured on adherent IgG which binds to the IL‐1 receptors. In our study we found that the pretreatment of cells with serial dilutions of IL‐1ra (250 ng/ml−2.5 pg/ml) inhibits, in a dose‐dependent manner, lymphocyte DNA synthesis stimulated with Con A (10 μg/ml). IL‐1ra did not have any effect on resting peripheral blood mononuclear cells (PBMC). Time course experiments show that IL‐1ra at 250 ng/ml has its maximum inhibitory effect on lymphocyte blastogenesis when cells are pretreated 2 h before Con A. No effect was found when hrIL‐1ra was added after Con A. Moreover, hrIL‐1ra also inhibits the enhancing effects of exogenous hrIL‐1 (400, 200, 100 and 50 ng/ml) on lymphocytes stimulated with Con A; while when hrIL‐1ra was used on cells treated with only Con A, the inhibition was more pronounced. When PBMC were removed from monocytes, by adherence, the Con A‐treated lymphocytes were not influenced by 2 h pretreatment of hrIL‐1ra; while a strong inhibition was found when exogenous hrIL‐1 was added at different concentrations. In addition, hrIL‐1ra also inhibits the enhancing effect of hrIL‐2 on lymphocyte DNA synthesis. In another set of experiments PBMC were pretreated with hrIL‐1ra (250 ng/ml) for 2 h and then added LPs (10 ng/ml) and IL‐1α generation was determined using ELISA. In these experiments IL‐1ra completely abolished the generation of IL‐1α. These data suggest that hrIL‐1ra exhibits a dose—response inhibition of lymphocyte blastogenesis induced by Con A, probably through the down‐regulation of IL‐1 synthesis necessary as an early signal for T‐cell activation and IL‐2 production.

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“…Fever and the other constitutional effects of human influenza (headache, myalgia, listlessness, nausea, shivering, anorexia and depression) appear to result from the production of a pyrogen [probably endogenous pyrogen (EP), but possibly interferon] by phagocytes in response to infection (Rawlins & Cranston, 1973;Scott et al, 1981;Dinarello & Wolff, 1982: Gander, 1982. This is supported by studies of influenza in the ferret using virulent (clones 7a and 64c) and attenuated [clone 64d and A/Puerto Rico/8/34 (PR/8)] strains of the A/Puerto Rico/8/34 A/England/939/69 reassortant virus system (Toms et al, 1977;Sweet et al, 1979;Matsuyama et al, 1980).…”

Section: Introductionmentioning

confidence: 99%

Severity of Fever in Influenza: Differential Pyrogenicity in Ferrets Exhibited by H1N1 and H3N2 Strains of Differing Virulence

Coates

Sweet

Smith

1986

Journal of General Virology

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SUMMARYIntracardial inoculation of large quantities (200 ~g viral protein/kg body weight) of infectious or u.v.-inactivated purified influenza viruses into ferrets resulted in a rapid febrile response which was significantly lower for two recently isolated H 1N 1 viruses, A/USSR/90/77 and A/Fiji/15899/83, than for two virulent clones, 7a and 64c, of the A/Puerto Rico/8/34 A/England/939/69 (H3N2) reassortant virus system. These results, which are in accord with the severity of fever produced by these strains in intranasally infected ferrets, show that influenza virus strains can differ in their capacity to induce fever (probably reflecting a differential capacity to induce endogenous pyrogen from phagocytes) and indicate, since u.v.-inactivated strains are pyrogenic, that this may be due to differences between strains in the nature or amount of certain virion components.

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Exogenous Pyrogens

Cited by 21 publications

References 163 publications

Influenza virus pyrogenicity: central role of structural orientation of virion components and involvement of viral lipid and glycoproteins

Influenza virus pyrogenicity: central role of structural orientation of virion components and involvement of viral lipid and glycoproteins

Human recombinant interleukin‐1 receptor antagonist inhibits lymphocyte blastogenesis induced by concanavalin A Restorative effect of hrIL‐1

Severity of Fever in Influenza: Differential Pyrogenicity in Ferrets Exhibited by H1N1 and H3N2 Strains of Differing Virulence

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