Essential fatty acid metabolism and immune function in disease states characterized by immunosuppression and abnormalities in lipid metabolism

Critical illness results in a plethora of metabolic and immunologic abnormalities. Essential fatty acids have profound effects on metabolism and immune function. During stress states there are perturbations in fatty acid metabolism that may alter the fatty acid composition immune cell membranes which impact on their cellular function. These functional changes may place the patient at risk for infection. Changes in lipid composition of neutrophils and lymphocytes that occur following burn injury and during cancer have not been characterized previously. Immune changes that have been reported to occur after burn injury, and during cancer and chemotherapy have not been examined in relation to membrane composition. The objective of this thesis research was to demonstrate that alterations in fatty acid composition of immune cells contribute to functional changes observed in both the cell mediated and innate immune branches in disease states characterized by metabolic impairments and immunosuppression. The disease states that were investigated included infection, burn injury, high dose chemotherapy for breast cancer and cachexic cancer patients who were fed supplemental fish oil. Immune measures performed using peripheral blood immune cells included lymphocyte proliferation and cytokine production in response to mitogens, NK cell cytotoxicity, neutrophil oxidative burst and characterization of lymphocyte phenotypes that were associated with membrane phospholipid changes. For each disease state, the discussion will focus on the relationship of immune measures to the arachidonic acid content in the immune cell membranes. A relationship between the arachidonic acid content of neutrophil membranes and their oxidative burst response was confirmed by an in vitro study. The implications of these findings in the design of nutritional intervention strategies aimed at up or down regulating specific immune functions will be discussed.