Doctoral Dissertations

Peter Mancuso

Date of Award

12-1996

Degree Type

Dissertation

Degree Name

Doctor of Philosophy

Major

Life Sciences

Major Professor

Michael D. Karlstad

Committee Members

Roger C. Carroll, Philip N. Bochsler, Jay Whelan

Abstract

Proinflammatory eicosanoids and cytokines are important mediators of inflammation in the adult respiratory distress syndrome. We investigated the effect of enteral nutrition with anti-inflammatory fatty acids, eicosapentaenoic acid and y-linolenic acid from fish and borage oil as compared with com oil on 1) lung microvascular permeability, mean arterial blood pressure, intrapulmonary synthesis of proinflammatory eicosanoids and cytokines, neutrophil accumulation, and platelet and white blood cell counts in endotoxin-induced lung injury, 2) alveolar macrophage prostaglandin and leukotriene synthesis, 3) liver, lung, and alveolar macrophage phospholipid fatty acid composition, 4) in a model of endotoxin-induced acute lung injury. Rats were randomized into four dietary treatment groups and fed nutritionally complete diets (300 kcal×kg-1×day-1) 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 permeability, mean arterial blood pressure, and white blood cell and platelet counts were determined 2 hours following iv injection of Salmonella enteritidls endotoxin (10 mg/kg). In a second group of rats, bronchoalveolar lavage was performed 2 hours following an iv injection of Salmonella enteritidls endotoxin (10 mg/kg) or saline. In a third group of rats alveolar macrophages were harvested from bronchoalveolar lavage fluid and stimulated in vitro with a calcium ionophore (A23187). Bronchoalveolar lavage fluid and alveolar macrophage cell culture media were analyzed for leukotrienes, thromboxane, and prostaglandins. Lung myeloperoxidase activity (a marker for neutrophil accumulation) and lung, liver and alveolar macrophage phospholipid fatty acids were also determined. Lung permeability was greatest with corn oil and significantly attenuated with 20% fish oil and 20% fish and 5% borage oil. Early and late hemodynamic insufficiency was attenuated with 20% fish oil and 20% fish and borage oil (5 and 20%) as compared with corn oil. Intrapulmonary leukotrienes 64 and C4/D4 and TXB2 and 6-keto-PGF1α, were significantly elevated with corn oil as compared with saline. In contrast, leukotrienes B4, and C4/D4, and TXB2, did not increase above those of saline in rats with 20% fish oil and 20% fish and 5% borage oil. Leukotriene B4, PGE2 and TXB2 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. Lung myeloperoxidase activity was significantly elevated with endotoxin treated rats as compared with their respective saline controls. Lung myeloperoxidase was significantly lower with 20% fish oil and 20% fish and 20% borage oil as compared with corn oil after endotoxin. Lung, liver, and alveolar macrophage levels of arachidonic acid were lower and the levels of eicosapentaenoic acid and docosahexaenoic acid were higher with 20% fish oil and 20% fish and 20% borage oil as compared with corn oil. Dihomo-γ-linolenic acid was elevated with 20% fish and 20% borage oil as compared with corn oil and 20% fish oil. These results indicate that dietary fish oil and fish and borage oil as compared with corn oil may have provided protection against endotoxin-induced increases in lung microvascular protein permeability and hemodynamic insufficiency by reducing the synthesis of intrapulmonary arachidonic acid derived proinflammatory eicosanoids and attenuating lung neutrophil accumulation.

Download
Files over 3MB may be slow to open. For best results, right-click and select "save as..."

Share

COinS