Comparison between effects of interleukin-1 alpha administration and sublethal endotoxemia in primates

Fischer, E.; Marano, Michael A.; Barber, Annabel; Hudson, Alan P.; Lee, K.; Rock, Craig S.; Hawes, A S; Thompson, R. C.; Hayes, Terence J.; Anderson, Timothy D.

doi:10.1152/ajpregu.1991.261.2.r442

Cited by 60 publications

(53 citation statements)

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“…On day 2, arterial blood was obtained at 6:00 a.m. (i.e., directly before the start of the infusion of epinephrine in the EPI-3 group or the start of saline infusion in the control group) ( t ϭ Ϫ 3 h), directly before the injection of endotoxin ( t ϭ 0 h), and 0.5, 1, 1.5, 2, 3, 4,5,6,8,12, and 24 h thereafter. All blood samples (except samples for leukocyte counts) were centrifuged at 4 Њ C for 20 min at 1,600 g and stored at Ϫ 70 Њ C until assayed.…”

Section: Methodsmentioning

confidence: 99%

“…It was therefore possible that epinephrine inhibits LPS-induced TNF production in whole blood at least in part by enhancing the release of IL-10. To test this hypothesis, we incubated whole blood for various time periods (4,8,12, and 16 h) with LPS (10 ng/ml) in the presence or absence of epinephrine (10 Ϫ6 M), a neutralizing anti-IL-10 mAb (25 g/ml) or an equivalent amount of an irrelevant isotype-matched control mAb. Anti-IL-10 potentiated LPSinduced TNF production, an effect that became significant after incubations of whole blood for 8 h or longer (Table I).…”

Section: Contribution Of ␣ and ␤ Adrenergic Receptors To Potentiationmentioning

confidence: 99%

See 1 more Smart Citation

Epinephrine inhibits tumor necrosis factor-alpha and potentiates interleukin 10 production during human endotoxemia.

Poll

Coyle²,

Barbosa³

et al. 1996

J. Clin. Invest.

473

225

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Short-term preexposure of mononuclear cells to epinephrine inhibits LPS-induced production of TNF, whereas preexposure for 24 h results in increased TNF production. To assess the effects of epinephrine infusions of varying duration on in vivo responses to LPS, the following experiments were performed: ( a ) Blood obtained from eight subjects at 4-24 h after the start of a 24-h infusion of epinephrine (30 ng/kg per min) produced less TNF after ex vivo stimulation with LPS compared with blood drawn before the start of the infusion, and ( b ) 17 healthy men who were receiving a continuous infusion of epinephrine (30 ng/kg per min) started either 3 h (EPI-3; n ϭ 5) or 24 h (EPI-24; n ϭ 6) before LPS injection or an infusion of normal saline (LPS; n ϭ 6) were studied after intravenous injection of LPS (2 ng/kg, lot EC-5). EPI-3 inhibited LPS-induced in vivo TNF appearance and also increased IL-10 release (both P Ͻ 0.005 versus LPS), whereas EPI-24 only attenuated TNF secretion ( P ϭ 0.05). In separate in vitro experiments in whole blood, epinephrine increased LPS-induced IL-10 release by a combined effect on ␣ and ␤ adrenergic receptors. Further, in LPS-stimulated blood, the increase in IL-10 levels caused by epinephrine only marginally contributed to concurrent inhibition of TNF production. Epinephrine, either endogenously produced or administered as a component of sepsis treatment, may have a net antiinflammatory effect on the cytokine network early in the course of systemic infection. ( J. Clin. Invest. 1996. 97:713-719.)

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Section: Methodsmentioning

confidence: 99%

Section: Contribution Of ␣ and ␤ Adrenergic Receptors To Potentiationmentioning

confidence: 99%

Epinephrine inhibits tumor necrosis factor-alpha and potentiates interleukin 10 production during human endotoxemia.

Poll

Coyle²,

Barbosa³

et al. 1996

J. Clin. Invest.

473

225

View full text Add to dashboard Cite

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“…We have recently reported that administration of recombinant human IL-la to healthy primates will result in hypotension and tachycardia similar to that seen in endotoxemia (6). Although quantities as low as 100 ng/kg body weight (BW) will produce significant tachycardia, 100 gg/kg BW of IL-la decreases cardiac output and causes adrenal cortex hemorrhage.…”

Section: Introductionmentioning

confidence: 96%

Interleukin-1 receptor blockade improves survival and hemodynamic performance in Escherichia coli septic shock, but fails to alter host responses to sublethal endotoxemia.

Fischer¹,

Marano²,

Zee³

et al. 1992

J. Clin. Invest.

325

118

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The present study was undertaken to evaluate the extent to which an endogenous interleukin-1 (IL-1) response contributes to the hemodynamic and metabolic consequences of sublethal endotoxemia or lethal Gram-negative septic shock. Young, healthy baboons received either a sublethal dose oflipopolysaccharide (LPS) or an LDIoo of live Escherichia coli bacteria, and one half of the animals in each group were continuously infused with IL-1 receptor antagonist (IL-ira). Plasma IL-/1# was not detected in this model of endotoxemia. Administration of ILira had only minimal effects on the modest hemodynamic and metabolic responses to sublethal endotoxemia, and did not attenuate the plasma cytokine response. In contrast, high circulating levels of IL-1iB (range 300800 pg/ml) were seen during lethal E. coli septic shock. IL-ira treatment significantly attenuated the decrease in mean arterial blood pressure (MAP) (from -72±8 to -43±6 mm Hg, P < 0.05) and cardiac output (from -0.81±0.17 to -0.48±0.15 liter/min; P < 0.05), and significantly improved survival from 43 to 100% at 24 h (P < 0.05). The plasma I-i1d and IL-6 responses to lethal E. coli septic shock were also significantly diminished by IL-ira treatment (P < 0.05), whereas tumor necrosis factor-a (TNFa) concentrations were unaffected. We conclude that an exaggerated systemic IL-1,6 response is characteristic of lethal E. coli septic shock, and contributes significantly to the hemodynamic and metabolic consequences of E. coli septic shock. IL-ira can significantly attenuate the cytokine cascade and improve survival. (J. Clin. Invest. 1992. 89:1551-1557.) Key words: tumor necrosis factor * interleukin-6 * interleukin-8 * lipopolysaccharide

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“…IL-1, -6, and -8 (23)(24)(25)(26), as well as TNF-lY, are also reduced during Il. -Lra administration (27), findings that may also account for the improvement in cardiac output and blood pressure in this model.…”

Section: Resultsmentioning

confidence: 99%

Effect of an Interleukin-1 Receptor Antagonist on the Hemodynamic Manifestations of Group B Streptococcal Sepsis

et al. 1995

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IL-1 is purported to be a proximal mediator in the cascade leading to septic shock. To characterize its hemodynamic effects and to ascertain whet her its block ade would ameliorat e the deleterious con sequences of sepsis, an IL-1 receptor antagonist (IL-1ra) was adminis tered to 16 anesthetized, mechanically ventilated piglets that rece ived a contin uous infusion of group B streptococci (GBS) (7.5 X 10 7 colony-forming units/kg/min ), Systemic (Psa), pulmonary artery (Ppa), and wedge (Pwp) pressures and cardiac output were measured pre-GBS and every 30 min during GBS infusion . After 15 min of bacteri al infusion the control group receiv ed norm al saline, whereas the treatment group rece ived a bolus of IL-1ra (40 mg/kg) followed by a con tinuo us infusion of IL-1ra (60 J-Lglkglmin). In comparing IL-lra-treated animals with controls from the IS-min GBS baseline to the succe eding septic study period (45-120 min), the following treatment effects were noted (120-min valu es shown) : mean Psa remained eleva ted in treatmen t compared with control animals (12.7 ::' ::: 2.5 versus 9 ::' ::: 3.5 kPa; p < 0.001) as did CO (0.21 ::' ::: 0.07 versus 0.13 ::' ::: 0.08 L'min/kg; p < 0.001) . Pwp decreased in the treatment comp ared to the con trol group over the study period (1 ::' ::: 0.3 versus 1.6 ::' ::: 0.7 kPa; p < 0.02). Mean IL-l is a cytokine thought to occupy a proximal position in the inflammatory cascade leading to tissue injury during sepsis (1, 2). After its release, IL-l influences the metabolism of arachidonic acid and results in increased synthesis of leukotrienes, prostaglandins, and thrombo xane A 2 (2). In addition, IL-l acts synergistica lly with other cytokines , such as TNFo:, to potentiate the inflammatory response (3).Investigators have focused on the role of IL-l as a prominent Ppa and mean Pra were not different between group s ove r time. Median length of sur vival was significantly longer (p = 0.04) in treated (226 min) comp ared with control animals (150 min). The se data suggest that IL-1 plays an impo rtant role in GBS sepsis and septic shock, and that IL-1ra may in part ameliorate the cardiovascular alterations associated with GBS sepsis in the neonate. (Pediatr Res 38: 704-708, 1995)

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Comparison between effects of interleukin-1 alpha administration and sublethal endotoxemia in primates

Cited by 60 publications

References 0 publications

Epinephrine inhibits tumor necrosis factor-alpha and potentiates interleukin 10 production during human endotoxemia.

Epinephrine inhibits tumor necrosis factor-alpha and potentiates interleukin 10 production during human endotoxemia.

Interleukin-1 receptor blockade improves survival and hemodynamic performance in Escherichia coli septic shock, but fails to alter host responses to sublethal endotoxemia.

Effect of an Interleukin-1 Receptor Antagonist on the Hemodynamic Manifestations of Group B Streptococcal Sepsis

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