Effects of eicosapentaenoic and γ-linolenic acid on lung permeability and alveolar macrophage eicosanoid synthesis in endotoxic rats

Peter Mancuso, Jay Whelan, Stephen J. DeMichele, Carolyn C. Snider, Julie A. Guszcza, Kate J. Claycombe, Gary T. Smith, Timothy J. Gregory, Michael Karlstad

Research output: Contribution to journalArticle

83 Citations (Scopus)

Abstract

Objectives: Proinflammatory eicosanoids (cyclooxygenase and lipoxygenase metabolites of arachidonic acid) released by alveolar macrophages play an important role in endotoxin-induced acute lung injury. We investigated the effect of prefeeding rats for 21 days with enteral diets that provided the anti-inflammatory fatty acids, eicosapentaenoic acid and γ-linolenic acid (derived from fish oil and borage oil, respectively), as compared with an n- 6 fatty acid-enriched diet (corn oil) on the following: a) lung microvascular protein permeability, arterial blood pressure, and platelet and white blood cells in a model of endotoxin-induced acute lung injury; b) alveolar macrophage prostaglandin and leukotriene synthesis; and c) liver and alveolar macrophage phospholipid fatty acid composition. Design: Prospective, randomized, controlled, double-blind study. Setting: Research laboratory at a university medical center. Subjects: Male Long-Evans rats, weighing 250 g. Interventions: Rats were randomized into four dietary treatment groups and fed nutritionally complete diets (300 kcal/kg/day), containing 55.2% of the total calories from fat with either 97% corn oil, 20% fish oil, 20% fish and 5% borage oil, or 20% fish and 20% borage oil for 21 days. On day 22, lung microvascular protein permeability, mean arterial pressure, and platelet and white blood cell counts were determined for 2 hrs after an intravenous injection of Salmonella enteritidis endotoxin (10 mg/kg). In a second group of prefed rats, the phospholipid fatty acid composition was determined in liver and alveolar macrophages. Alveolar macrophages were harvested by bronchoalveolar lavage and stimulated in vitro with a calcium ionophore (A23187), and the concentrations of leukotrienes B4 and B5, thromboxane A2, prostaglandin E2, and 6-keto-prostaglandin F(1α) were measured in a third group of prefed rats. Measurements and Main Results: Lung permeability was greatest with corn oil and was significantly attenuated with 20% fish oil and 20% fish and 5% borage oil, and this effect approached significance with 20% fish and 20% borage oil (p = .06). The early and late hypotensive effects of endotoxin were attenuated with 20% fish oil, 20% fish and 5% borage oil, and 20% fish and 20% borage oil, as compared with corn oil. Concentrations of leukotriene B4, prostaglandin E2, and thromboxane B2 released from A23187- stimulated alveolar macrophages were significantly lower with 20% fish oil and 20% fish and 20% borage oil, as compared with corn oil. The increase in lung microvascular protein permeability with 20% fish and 20% borage oil was not significantly different than the lung microvascular protein permeability that was found in animals receiving 20% fish oil (p = .20) and 20% fish and 5% borage oil (p = .31). Alveolar macrophage and liver phospholipid concentrations of arachidonic acid were lower, and the concentrations of eicosapentaenoic acid and docosahexaenoic acid were higher, with 20% fish oil, 20% fish and 5% borage oil, and 20% fish and 20% borage oil, as compared with corn oil. Dihomo-γ-linolenic acid, the desaturated and elongated intermediate of γ-linolenic acid, was increased with 20% fish and 20% borage oil, as compared with 20% fish oil and 20% fish and 5% borage oil. Conclusions: The severity of pulmonary microvascular protein permeability and the degree of hypotension were reduced with fish or fish and borage oil diets, as compared with corn oil, in endotoxic rats. The reduced synthesis of the proinflammatory arachidonic acid-derived mediators, leukotriene B4, thromboxane B2, and prostaglandin E2 from stimulated alveolar macrophages was indicative of a decrease in arachidonic acid and an increase in eicosapentaenoic acid and docosahexaenoic acid in cell membrane phospholipids. The modulation of proinflammatory eicosanoid synthesis with anti-inflammatory fatty acids, eicosapentaenoic acid, and docosapentaenoic acid and γ-linolenic acid, may have reduced the severity of pulmonary permeability and hypotension after endotoxin administration.

Original languageEnglish (US)
Pages (from-to)523-532
Number of pages10
JournalCritical Care Medicine
Volume25
Issue number3
DOIs
StatePublished - Mar 1 1997

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alpha-Linolenic Acid
Eicosanoids
Alveolar Macrophages
Permeability
Fishes
Fish Oils
Lung
Corn Oil
Capillary Permeability
Eicosapentaenoic Acid
Fatty Acids
Endotoxins
Leukotriene B4
Phospholipids
Dinoprostone
Arachidonic Acid
Diet
Thromboxane B2
Docosahexaenoic Acids
Acute Lung Injury

All Science Journal Classification (ASJC) codes

  • Critical Care and Intensive Care Medicine

Cite this

Effects of eicosapentaenoic and γ-linolenic acid on lung permeability and alveolar macrophage eicosanoid synthesis in endotoxic rats. / Mancuso, Peter; Whelan, Jay; DeMichele, Stephen J.; Snider, Carolyn C.; Guszcza, Julie A.; Claycombe, Kate J.; Smith, Gary T.; Gregory, Timothy J.; Karlstad, Michael.

In: Critical Care Medicine, Vol. 25, No. 3, 01.03.1997, p. 523-532.

Research output: Contribution to journalArticle

Mancuso, Peter ; Whelan, Jay ; DeMichele, Stephen J. ; Snider, Carolyn C. ; Guszcza, Julie A. ; Claycombe, Kate J. ; Smith, Gary T. ; Gregory, Timothy J. ; Karlstad, Michael. / Effects of eicosapentaenoic and γ-linolenic acid on lung permeability and alveolar macrophage eicosanoid synthesis in endotoxic rats. In: Critical Care Medicine. 1997 ; Vol. 25, No. 3. pp. 523-532.
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abstract = "Objectives: Proinflammatory eicosanoids (cyclooxygenase and lipoxygenase metabolites of arachidonic acid) released by alveolar macrophages play an important role in endotoxin-induced acute lung injury. We investigated the effect of prefeeding rats for 21 days with enteral diets that provided the anti-inflammatory fatty acids, eicosapentaenoic acid and γ-linolenic acid (derived from fish oil and borage oil, respectively), as compared with an n- 6 fatty acid-enriched diet (corn oil) on the following: a) lung microvascular protein permeability, arterial blood pressure, and platelet and white blood cells in a model of endotoxin-induced acute lung injury; b) alveolar macrophage prostaglandin and leukotriene synthesis; and c) liver and alveolar macrophage phospholipid fatty acid composition. Design: Prospective, randomized, controlled, double-blind study. Setting: Research laboratory at a university medical center. Subjects: Male Long-Evans rats, weighing 250 g. Interventions: Rats were randomized into four dietary treatment groups and fed nutritionally complete diets (300 kcal/kg/day), containing 55.2{\%} of the total calories from fat with either 97{\%} corn oil, 20{\%} fish oil, 20{\%} fish and 5{\%} borage oil, or 20{\%} fish and 20{\%} borage oil for 21 days. On day 22, lung microvascular protein permeability, mean arterial pressure, and platelet and white blood cell counts were determined for 2 hrs after an intravenous injection of Salmonella enteritidis endotoxin (10 mg/kg). In a second group of prefed rats, the phospholipid fatty acid composition was determined in liver and alveolar macrophages. Alveolar macrophages were harvested by bronchoalveolar lavage and stimulated in vitro with a calcium ionophore (A23187), and the concentrations of leukotrienes B4 and B5, thromboxane A2, prostaglandin E2, and 6-keto-prostaglandin F(1α) were measured in a third group of prefed rats. Measurements and Main Results: Lung permeability was greatest with corn oil and was significantly attenuated with 20{\%} fish oil and 20{\%} fish and 5{\%} borage oil, and this effect approached significance with 20{\%} fish and 20{\%} borage oil (p = .06). The early and late hypotensive effects of endotoxin were attenuated with 20{\%} fish oil, 20{\%} fish and 5{\%} borage oil, and 20{\%} fish and 20{\%} borage oil, as compared with corn oil. Concentrations of leukotriene B4, prostaglandin E2, and thromboxane B2 released from A23187- stimulated alveolar macrophages were significantly lower with 20{\%} fish oil and 20{\%} fish and 20{\%} borage oil, as compared with corn oil. The increase in lung microvascular protein permeability with 20{\%} fish and 20{\%} borage oil was not significantly different than the lung microvascular protein permeability that was found in animals receiving 20{\%} fish oil (p = .20) and 20{\%} fish and 5{\%} borage oil (p = .31). Alveolar macrophage and liver phospholipid concentrations of arachidonic acid were lower, and the concentrations of eicosapentaenoic acid and docosahexaenoic acid were higher, with 20{\%} fish oil, 20{\%} fish and 5{\%} borage oil, and 20{\%} fish and 20{\%} borage oil, as compared with corn oil. Dihomo-γ-linolenic acid, the desaturated and elongated intermediate of γ-linolenic acid, was increased with 20{\%} fish and 20{\%} borage oil, as compared with 20{\%} fish oil and 20{\%} fish and 5{\%} borage oil. Conclusions: The severity of pulmonary microvascular protein permeability and the degree of hypotension were reduced with fish or fish and borage oil diets, as compared with corn oil, in endotoxic rats. The reduced synthesis of the proinflammatory arachidonic acid-derived mediators, leukotriene B4, thromboxane B2, and prostaglandin E2 from stimulated alveolar macrophages was indicative of a decrease in arachidonic acid and an increase in eicosapentaenoic acid and docosahexaenoic acid in cell membrane phospholipids. The modulation of proinflammatory eicosanoid synthesis with anti-inflammatory fatty acids, eicosapentaenoic acid, and docosapentaenoic acid and γ-linolenic acid, may have reduced the severity of pulmonary permeability and hypotension after endotoxin administration.",
author = "Peter Mancuso and Jay Whelan and DeMichele, {Stephen J.} and Snider, {Carolyn C.} and Guszcza, {Julie A.} and Claycombe, {Kate J.} and Smith, {Gary T.} and Gregory, {Timothy J.} and Michael Karlstad",
year = "1997",
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TY - JOUR

T1 - Effects of eicosapentaenoic and γ-linolenic acid on lung permeability and alveolar macrophage eicosanoid synthesis in endotoxic rats

AU - Mancuso, Peter

AU - Whelan, Jay

AU - DeMichele, Stephen J.

AU - Snider, Carolyn C.

AU - Guszcza, Julie A.

AU - Claycombe, Kate J.

AU - Smith, Gary T.

AU - Gregory, Timothy J.

AU - Karlstad, Michael

PY - 1997/3/1

Y1 - 1997/3/1

N2 - Objectives: Proinflammatory eicosanoids (cyclooxygenase and lipoxygenase metabolites of arachidonic acid) released by alveolar macrophages play an important role in endotoxin-induced acute lung injury. We investigated the effect of prefeeding rats for 21 days with enteral diets that provided the anti-inflammatory fatty acids, eicosapentaenoic acid and γ-linolenic acid (derived from fish oil and borage oil, respectively), as compared with an n- 6 fatty acid-enriched diet (corn oil) on the following: a) lung microvascular protein permeability, arterial blood pressure, and platelet and white blood cells in a model of endotoxin-induced acute lung injury; b) alveolar macrophage prostaglandin and leukotriene synthesis; and c) liver and alveolar macrophage phospholipid fatty acid composition. Design: Prospective, randomized, controlled, double-blind study. Setting: Research laboratory at a university medical center. Subjects: Male Long-Evans rats, weighing 250 g. Interventions: Rats were randomized into four dietary treatment groups and fed nutritionally complete diets (300 kcal/kg/day), containing 55.2% of the total calories from fat with either 97% corn oil, 20% fish oil, 20% fish and 5% borage oil, or 20% fish and 20% borage oil for 21 days. On day 22, lung microvascular protein permeability, mean arterial pressure, and platelet and white blood cell counts were determined for 2 hrs after an intravenous injection of Salmonella enteritidis endotoxin (10 mg/kg). In a second group of prefed rats, the phospholipid fatty acid composition was determined in liver and alveolar macrophages. Alveolar macrophages were harvested by bronchoalveolar lavage and stimulated in vitro with a calcium ionophore (A23187), and the concentrations of leukotrienes B4 and B5, thromboxane A2, prostaglandin E2, and 6-keto-prostaglandin F(1α) were measured in a third group of prefed rats. Measurements and Main Results: Lung permeability was greatest with corn oil and was significantly attenuated with 20% fish oil and 20% fish and 5% borage oil, and this effect approached significance with 20% fish and 20% borage oil (p = .06). The early and late hypotensive effects of endotoxin were attenuated with 20% fish oil, 20% fish and 5% borage oil, and 20% fish and 20% borage oil, as compared with corn oil. Concentrations of leukotriene B4, prostaglandin E2, and thromboxane B2 released from A23187- stimulated alveolar macrophages were significantly lower with 20% fish oil and 20% fish and 20% borage oil, as compared with corn oil. The increase in lung microvascular protein permeability with 20% fish and 20% borage oil was not significantly different than the lung microvascular protein permeability that was found in animals receiving 20% fish oil (p = .20) and 20% fish and 5% borage oil (p = .31). Alveolar macrophage and liver phospholipid concentrations of arachidonic acid were lower, and the concentrations of eicosapentaenoic acid and docosahexaenoic acid were higher, with 20% fish oil, 20% fish and 5% borage oil, and 20% fish and 20% borage oil, as compared with corn oil. Dihomo-γ-linolenic acid, the desaturated and elongated intermediate of γ-linolenic acid, was increased with 20% fish and 20% borage oil, as compared with 20% fish oil and 20% fish and 5% borage oil. Conclusions: The severity of pulmonary microvascular protein permeability and the degree of hypotension were reduced with fish or fish and borage oil diets, as compared with corn oil, in endotoxic rats. The reduced synthesis of the proinflammatory arachidonic acid-derived mediators, leukotriene B4, thromboxane B2, and prostaglandin E2 from stimulated alveolar macrophages was indicative of a decrease in arachidonic acid and an increase in eicosapentaenoic acid and docosahexaenoic acid in cell membrane phospholipids. The modulation of proinflammatory eicosanoid synthesis with anti-inflammatory fatty acids, eicosapentaenoic acid, and docosapentaenoic acid and γ-linolenic acid, may have reduced the severity of pulmonary permeability and hypotension after endotoxin administration.

AB - Objectives: Proinflammatory eicosanoids (cyclooxygenase and lipoxygenase metabolites of arachidonic acid) released by alveolar macrophages play an important role in endotoxin-induced acute lung injury. We investigated the effect of prefeeding rats for 21 days with enteral diets that provided the anti-inflammatory fatty acids, eicosapentaenoic acid and γ-linolenic acid (derived from fish oil and borage oil, respectively), as compared with an n- 6 fatty acid-enriched diet (corn oil) on the following: a) lung microvascular protein permeability, arterial blood pressure, and platelet and white blood cells in a model of endotoxin-induced acute lung injury; b) alveolar macrophage prostaglandin and leukotriene synthesis; and c) liver and alveolar macrophage phospholipid fatty acid composition. Design: Prospective, randomized, controlled, double-blind study. Setting: Research laboratory at a university medical center. Subjects: Male Long-Evans rats, weighing 250 g. Interventions: Rats were randomized into four dietary treatment groups and fed nutritionally complete diets (300 kcal/kg/day), containing 55.2% of the total calories from fat with either 97% corn oil, 20% fish oil, 20% fish and 5% borage oil, or 20% fish and 20% borage oil for 21 days. On day 22, lung microvascular protein permeability, mean arterial pressure, and platelet and white blood cell counts were determined for 2 hrs after an intravenous injection of Salmonella enteritidis endotoxin (10 mg/kg). In a second group of prefed rats, the phospholipid fatty acid composition was determined in liver and alveolar macrophages. Alveolar macrophages were harvested by bronchoalveolar lavage and stimulated in vitro with a calcium ionophore (A23187), and the concentrations of leukotrienes B4 and B5, thromboxane A2, prostaglandin E2, and 6-keto-prostaglandin F(1α) were measured in a third group of prefed rats. Measurements and Main Results: Lung permeability was greatest with corn oil and was significantly attenuated with 20% fish oil and 20% fish and 5% borage oil, and this effect approached significance with 20% fish and 20% borage oil (p = .06). The early and late hypotensive effects of endotoxin were attenuated with 20% fish oil, 20% fish and 5% borage oil, and 20% fish and 20% borage oil, as compared with corn oil. Concentrations of leukotriene B4, prostaglandin E2, and thromboxane B2 released from A23187- stimulated alveolar macrophages were significantly lower with 20% fish oil and 20% fish and 20% borage oil, as compared with corn oil. The increase in lung microvascular protein permeability with 20% fish and 20% borage oil was not significantly different than the lung microvascular protein permeability that was found in animals receiving 20% fish oil (p = .20) and 20% fish and 5% borage oil (p = .31). Alveolar macrophage and liver phospholipid concentrations of arachidonic acid were lower, and the concentrations of eicosapentaenoic acid and docosahexaenoic acid were higher, with 20% fish oil, 20% fish and 5% borage oil, and 20% fish and 20% borage oil, as compared with corn oil. Dihomo-γ-linolenic acid, the desaturated and elongated intermediate of γ-linolenic acid, was increased with 20% fish and 20% borage oil, as compared with 20% fish oil and 20% fish and 5% borage oil. Conclusions: The severity of pulmonary microvascular protein permeability and the degree of hypotension were reduced with fish or fish and borage oil diets, as compared with corn oil, in endotoxic rats. The reduced synthesis of the proinflammatory arachidonic acid-derived mediators, leukotriene B4, thromboxane B2, and prostaglandin E2 from stimulated alveolar macrophages was indicative of a decrease in arachidonic acid and an increase in eicosapentaenoic acid and docosahexaenoic acid in cell membrane phospholipids. The modulation of proinflammatory eicosanoid synthesis with anti-inflammatory fatty acids, eicosapentaenoic acid, and docosapentaenoic acid and γ-linolenic acid, may have reduced the severity of pulmonary permeability and hypotension after endotoxin administration.

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