Are events after endotoxemia related to circulating phospholipase A2?

Alfred A. Santos, Jeffrey L. Browning, Marcus R. Scheltinga, Elizabeth A. Lynch, Elaine F. Brown, Pornsi Lawton, Elizabeth Chambers, Irene Dougas, Christopher D. Benjamin, Charles A. Dinarello, Sheldon M. Wolff, Danny O. Jacobs, Douglas W. Wilmore

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

Objective: The authors sought to determine whether the signs and symptoms of endotoxemia were related to the endotoxin-stimulated increase in circulating phospholipase A2 (PLA2) activity. Background: Because hypotension and pulmonary injury have been associated with elevated PLA2 activity in septic shock and PLA2 levels are reduced with the administration of glucocorticoids, the PLA2 response to endotoxin was investigated in volunteers pretreated with and without hydrocortisone. Methods: Carefully screened human subjects were studied under four conditions: (1) saline, (2) hydrocortisone, (3) endotoxin, and (4) hydrocortisone administration before endotoxin exposure. Pulse rate, blood pressure, temperature, and symptoms of endotoxemia were serially measured. Plasma for tumor necrosis factor concentrations and PLA2 activity was obtained. Results: After lipopolysaccharide, pulse rate and tumor necrosis factor concentrations rose at 1 to 2 hours; temperature increased maximally at 4 hours. PLA2 activity reached peak levels at 24 hours. With hydrocortisone pretreatment, a 50% reduction in the concentrations of tumor necrosis factor and PLA2 occurred. Significant correlations between other variables and PLA2 activity were not observed. The enzyme identified by monoclonal antibody was the secreted nonpancreatic PLA2 (SNP-PLA2). Conclusions: The results of this study suggest that elevations in circulating SNP-PLA2 activity and systemic events associated with intravenous endotoxin administration are unrelated.

Original languageEnglish (US)
Pages (from-to)183-192
Number of pages10
JournalAnnals of Surgery
Volume219
Issue number2
StatePublished - Feb 1994
Externally publishedYes

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Endotoxemia
Phospholipases A2
Endotoxins
Hydrocortisone
Tumor Necrosis Factor-alpha
Heart Rate
Secretory Phospholipase A2
Temperature
Lung Injury
Septic Shock
Intravenous Administration
Hypotension
Glucocorticoids
Signs and Symptoms
Lipopolysaccharides
Volunteers
Monoclonal Antibodies
Blood Pressure
Enzymes

ASJC Scopus subject areas

  • Surgery

Cite this

Santos, A. A., Browning, J. L., Scheltinga, M. R., Lynch, E. A., Brown, E. F., Lawton, P., ... Wilmore, D. W. (1994). Are events after endotoxemia related to circulating phospholipase A2? Annals of Surgery, 219(2), 183-192.

Are events after endotoxemia related to circulating phospholipase A2? / Santos, Alfred A.; Browning, Jeffrey L.; Scheltinga, Marcus R.; Lynch, Elizabeth A.; Brown, Elaine F.; Lawton, Pornsi; Chambers, Elizabeth; Dougas, Irene; Benjamin, Christopher D.; Dinarello, Charles A.; Wolff, Sheldon M.; Jacobs, Danny O.; Wilmore, Douglas W.

In: Annals of Surgery, Vol. 219, No. 2, 02.1994, p. 183-192.

Research output: Contribution to journalArticle

Santos, AA, Browning, JL, Scheltinga, MR, Lynch, EA, Brown, EF, Lawton, P, Chambers, E, Dougas, I, Benjamin, CD, Dinarello, CA, Wolff, SM, Jacobs, DO & Wilmore, DW 1994, 'Are events after endotoxemia related to circulating phospholipase A2?', Annals of Surgery, vol. 219, no. 2, pp. 183-192.
Santos AA, Browning JL, Scheltinga MR, Lynch EA, Brown EF, Lawton P et al. Are events after endotoxemia related to circulating phospholipase A2? Annals of Surgery. 1994 Feb;219(2):183-192.
Santos, Alfred A. ; Browning, Jeffrey L. ; Scheltinga, Marcus R. ; Lynch, Elizabeth A. ; Brown, Elaine F. ; Lawton, Pornsi ; Chambers, Elizabeth ; Dougas, Irene ; Benjamin, Christopher D. ; Dinarello, Charles A. ; Wolff, Sheldon M. ; Jacobs, Danny O. ; Wilmore, Douglas W. / Are events after endotoxemia related to circulating phospholipase A2?. In: Annals of Surgery. 1994 ; Vol. 219, No. 2. pp. 183-192.
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abstract = "Objective: The authors sought to determine whether the signs and symptoms of endotoxemia were related to the endotoxin-stimulated increase in circulating phospholipase A2 (PLA2) activity. Background: Because hypotension and pulmonary injury have been associated with elevated PLA2 activity in septic shock and PLA2 levels are reduced with the administration of glucocorticoids, the PLA2 response to endotoxin was investigated in volunteers pretreated with and without hydrocortisone. Methods: Carefully screened human subjects were studied under four conditions: (1) saline, (2) hydrocortisone, (3) endotoxin, and (4) hydrocortisone administration before endotoxin exposure. Pulse rate, blood pressure, temperature, and symptoms of endotoxemia were serially measured. Plasma for tumor necrosis factor concentrations and PLA2 activity was obtained. Results: After lipopolysaccharide, pulse rate and tumor necrosis factor concentrations rose at 1 to 2 hours; temperature increased maximally at 4 hours. PLA2 activity reached peak levels at 24 hours. With hydrocortisone pretreatment, a 50{\%} reduction in the concentrations of tumor necrosis factor and PLA2 occurred. Significant correlations between other variables and PLA2 activity were not observed. The enzyme identified by monoclonal antibody was the secreted nonpancreatic PLA2 (SNP-PLA2). Conclusions: The results of this study suggest that elevations in circulating SNP-PLA2 activity and systemic events associated with intravenous endotoxin administration are unrelated.",
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