Diphosphoryl lipid A from Rhodopseudomonas sphaeroides induces tolerance to endotoxic shock in the rat

C. M. Carpati, M. E. Astiz, Dhanonjoy C. Saha, E. C. Rackow

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Objectives: To examine the hemodynamic effects of diphosphoryl lipid A from Rhodopseudomonas sphaeroides and to examine the ability of this substance to induce tolerance to endotoxic shock. Design: Randomized, prospective, controlled study comparing the hemodynamic actions of R. sphaeroides diphosphoryl lipid A to those effects of lipopolysaccharide from Salmonella minnesota, followed by a prospective, randomized, controlled study comparing pretreatment with R. sphaeroides diphosphoryl lipid A and phosphate-buffered saline in the induction of tolerance to endotoxic shock. Setting: Laboratory of the Section of Critical Care Medicine at a University Hospital. Subjects: Male Sprague-Dawley rats. Interventions: Eight rats were randomized to receive intravenous R. sphaeroides diphosphoryl lipid A, 0.5 mg/100 g body weight or S. minnesota lipopolysaccharide, 0.5 mg/100 g body weight. Ten rats were then randomized to receive R. sphaeroides diphosphoryl lipid A, 0.5 mg/100 g body weight, or phosphate-buffered saline intravenously 48 hrs before receiving S. minnesota lipopolysaccharide, 5 mg/100 g body weight, by intravenous infusion. Measurements and Main Results: Cardiac index was significantly decreased from baseline in rats treated with lipopolysaccharide; there was no significant change in the R. sphaeroides diphosphoryl lipid A group. Peak circulating tumor necrosis factor (TNF) concentrations in the lipopolysaccharide-treated rats were higher than in R. sphaeroides diphosphoryl lipid A-treated rats (3.1 ± 1.0 vs. 1.5 ± 0.4 ng/mL). R. sphaeroides diphosphoryl lipid A significantly attenuated lipopolysaccharide-induced changes in mean arterial pressure and cardiac index. At baseline, there was no significant difference in serum TNF concentrations between rats pretreated with R. sphaeroides diphosphoryl lipid A and those rats pretreated with phosphate-buffered saline. TNF levels peaked at 1 hr post-lipopolysaccharide infusion at 4.3 ± 0.6 ng/mL in the phosphate-buffered saline group and at 2.0 ± 0.5 ng/mL in the R. sphaeroides diphosphoryl lipid A group (p <.02). Four of five rats pretreated with R. sphaeroides diphosphoryl lipid A survived endotoxic shock, whereas none of the phosphate-buffered saline-pretreated rats survived (p = .05). Conclusions: These observations are consistent with previous reports of the limited toxic effects of R. sphaeroides diphosphoryl lipid A and suggest that this molecule retains the ability to induce tolerance to endotoxic shock.

Original languageEnglish (US)
Pages (from-to)753-758
Number of pages6
JournalCritical Care Medicine
Volume21
Issue number5
StatePublished - 1993
Externally publishedYes

Fingerprint

Rhodobacter sphaeroides
Septic Shock
Lipopolysaccharides
Phosphates
Body Weight
Tumor Necrosis Factor-alpha
diphosphoryl lipid A
Hemodynamics
Poisons
Critical Care
Intravenous Infusions
Salmonella
Sprague Dawley Rats
Arterial Pressure

Keywords

  • bacterial infections
  • critical illness
  • cytokines
  • endotoxin
  • Gram- negative
  • lipid A
  • lipopolysaccharide
  • Rhodopseudomonas sphaeroides
  • septic shock
  • shock
  • tumor necrosis factor

ASJC Scopus subject areas

  • Critical Care and Intensive Care Medicine

Cite this

Diphosphoryl lipid A from Rhodopseudomonas sphaeroides induces tolerance to endotoxic shock in the rat. / Carpati, C. M.; Astiz, M. E.; Saha, Dhanonjoy C.; Rackow, E. C.

In: Critical Care Medicine, Vol. 21, No. 5, 1993, p. 753-758.

Research output: Contribution to journalArticle

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abstract = "Objectives: To examine the hemodynamic effects of diphosphoryl lipid A from Rhodopseudomonas sphaeroides and to examine the ability of this substance to induce tolerance to endotoxic shock. Design: Randomized, prospective, controlled study comparing the hemodynamic actions of R. sphaeroides diphosphoryl lipid A to those effects of lipopolysaccharide from Salmonella minnesota, followed by a prospective, randomized, controlled study comparing pretreatment with R. sphaeroides diphosphoryl lipid A and phosphate-buffered saline in the induction of tolerance to endotoxic shock. Setting: Laboratory of the Section of Critical Care Medicine at a University Hospital. Subjects: Male Sprague-Dawley rats. Interventions: Eight rats were randomized to receive intravenous R. sphaeroides diphosphoryl lipid A, 0.5 mg/100 g body weight or S. minnesota lipopolysaccharide, 0.5 mg/100 g body weight. Ten rats were then randomized to receive R. sphaeroides diphosphoryl lipid A, 0.5 mg/100 g body weight, or phosphate-buffered saline intravenously 48 hrs before receiving S. minnesota lipopolysaccharide, 5 mg/100 g body weight, by intravenous infusion. Measurements and Main Results: Cardiac index was significantly decreased from baseline in rats treated with lipopolysaccharide; there was no significant change in the R. sphaeroides diphosphoryl lipid A group. Peak circulating tumor necrosis factor (TNF) concentrations in the lipopolysaccharide-treated rats were higher than in R. sphaeroides diphosphoryl lipid A-treated rats (3.1 ± 1.0 vs. 1.5 ± 0.4 ng/mL). R. sphaeroides diphosphoryl lipid A significantly attenuated lipopolysaccharide-induced changes in mean arterial pressure and cardiac index. At baseline, there was no significant difference in serum TNF concentrations between rats pretreated with R. sphaeroides diphosphoryl lipid A and those rats pretreated with phosphate-buffered saline. TNF levels peaked at 1 hr post-lipopolysaccharide infusion at 4.3 ± 0.6 ng/mL in the phosphate-buffered saline group and at 2.0 ± 0.5 ng/mL in the R. sphaeroides diphosphoryl lipid A group (p <.02). Four of five rats pretreated with R. sphaeroides diphosphoryl lipid A survived endotoxic shock, whereas none of the phosphate-buffered saline-pretreated rats survived (p = .05). Conclusions: These observations are consistent with previous reports of the limited toxic effects of R. sphaeroides diphosphoryl lipid A and suggest that this molecule retains the ability to induce tolerance to endotoxic shock.",
keywords = "bacterial infections, critical illness, cytokines, endotoxin, Gram- negative, lipid A, lipopolysaccharide, Rhodopseudomonas sphaeroides, septic shock, shock, tumor necrosis factor",
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T1 - Diphosphoryl lipid A from Rhodopseudomonas sphaeroides induces tolerance to endotoxic shock in the rat

AU - Carpati, C. M.

AU - Astiz, M. E.

AU - Saha, Dhanonjoy C.

AU - Rackow, E. C.

PY - 1993

Y1 - 1993

N2 - Objectives: To examine the hemodynamic effects of diphosphoryl lipid A from Rhodopseudomonas sphaeroides and to examine the ability of this substance to induce tolerance to endotoxic shock. Design: Randomized, prospective, controlled study comparing the hemodynamic actions of R. sphaeroides diphosphoryl lipid A to those effects of lipopolysaccharide from Salmonella minnesota, followed by a prospective, randomized, controlled study comparing pretreatment with R. sphaeroides diphosphoryl lipid A and phosphate-buffered saline in the induction of tolerance to endotoxic shock. Setting: Laboratory of the Section of Critical Care Medicine at a University Hospital. Subjects: Male Sprague-Dawley rats. Interventions: Eight rats were randomized to receive intravenous R. sphaeroides diphosphoryl lipid A, 0.5 mg/100 g body weight or S. minnesota lipopolysaccharide, 0.5 mg/100 g body weight. Ten rats were then randomized to receive R. sphaeroides diphosphoryl lipid A, 0.5 mg/100 g body weight, or phosphate-buffered saline intravenously 48 hrs before receiving S. minnesota lipopolysaccharide, 5 mg/100 g body weight, by intravenous infusion. Measurements and Main Results: Cardiac index was significantly decreased from baseline in rats treated with lipopolysaccharide; there was no significant change in the R. sphaeroides diphosphoryl lipid A group. Peak circulating tumor necrosis factor (TNF) concentrations in the lipopolysaccharide-treated rats were higher than in R. sphaeroides diphosphoryl lipid A-treated rats (3.1 ± 1.0 vs. 1.5 ± 0.4 ng/mL). R. sphaeroides diphosphoryl lipid A significantly attenuated lipopolysaccharide-induced changes in mean arterial pressure and cardiac index. At baseline, there was no significant difference in serum TNF concentrations between rats pretreated with R. sphaeroides diphosphoryl lipid A and those rats pretreated with phosphate-buffered saline. TNF levels peaked at 1 hr post-lipopolysaccharide infusion at 4.3 ± 0.6 ng/mL in the phosphate-buffered saline group and at 2.0 ± 0.5 ng/mL in the R. sphaeroides diphosphoryl lipid A group (p <.02). Four of five rats pretreated with R. sphaeroides diphosphoryl lipid A survived endotoxic shock, whereas none of the phosphate-buffered saline-pretreated rats survived (p = .05). Conclusions: These observations are consistent with previous reports of the limited toxic effects of R. sphaeroides diphosphoryl lipid A and suggest that this molecule retains the ability to induce tolerance to endotoxic shock.

AB - Objectives: To examine the hemodynamic effects of diphosphoryl lipid A from Rhodopseudomonas sphaeroides and to examine the ability of this substance to induce tolerance to endotoxic shock. Design: Randomized, prospective, controlled study comparing the hemodynamic actions of R. sphaeroides diphosphoryl lipid A to those effects of lipopolysaccharide from Salmonella minnesota, followed by a prospective, randomized, controlled study comparing pretreatment with R. sphaeroides diphosphoryl lipid A and phosphate-buffered saline in the induction of tolerance to endotoxic shock. Setting: Laboratory of the Section of Critical Care Medicine at a University Hospital. Subjects: Male Sprague-Dawley rats. Interventions: Eight rats were randomized to receive intravenous R. sphaeroides diphosphoryl lipid A, 0.5 mg/100 g body weight or S. minnesota lipopolysaccharide, 0.5 mg/100 g body weight. Ten rats were then randomized to receive R. sphaeroides diphosphoryl lipid A, 0.5 mg/100 g body weight, or phosphate-buffered saline intravenously 48 hrs before receiving S. minnesota lipopolysaccharide, 5 mg/100 g body weight, by intravenous infusion. Measurements and Main Results: Cardiac index was significantly decreased from baseline in rats treated with lipopolysaccharide; there was no significant change in the R. sphaeroides diphosphoryl lipid A group. Peak circulating tumor necrosis factor (TNF) concentrations in the lipopolysaccharide-treated rats were higher than in R. sphaeroides diphosphoryl lipid A-treated rats (3.1 ± 1.0 vs. 1.5 ± 0.4 ng/mL). R. sphaeroides diphosphoryl lipid A significantly attenuated lipopolysaccharide-induced changes in mean arterial pressure and cardiac index. At baseline, there was no significant difference in serum TNF concentrations between rats pretreated with R. sphaeroides diphosphoryl lipid A and those rats pretreated with phosphate-buffered saline. TNF levels peaked at 1 hr post-lipopolysaccharide infusion at 4.3 ± 0.6 ng/mL in the phosphate-buffered saline group and at 2.0 ± 0.5 ng/mL in the R. sphaeroides diphosphoryl lipid A group (p <.02). Four of five rats pretreated with R. sphaeroides diphosphoryl lipid A survived endotoxic shock, whereas none of the phosphate-buffered saline-pretreated rats survived (p = .05). Conclusions: These observations are consistent with previous reports of the limited toxic effects of R. sphaeroides diphosphoryl lipid A and suggest that this molecule retains the ability to induce tolerance to endotoxic shock.

KW - bacterial infections

KW - critical illness

KW - cytokines

KW - endotoxin

KW - Gram- negative

KW - lipid A

KW - lipopolysaccharide

KW - Rhodopseudomonas sphaeroides

KW - septic shock

KW - shock

KW - tumor necrosis factor

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JF - Critical Care Medicine

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