Incidence and severity of dairy cow disease is greatest in the periparturient period. Mobilization of saturated and unsaturated fatty acids from adipose tissue into plasma is a well-established risk factor for periparturient disease. Lipid mobilization was associated with changes in peripheral leukocyte content of polyunsaturated fatty acids and could impact production of the mediators of inflammatory pathways known as oxylipids. Previous bovine leukocyte studies associated expression of some proinflammatory markers and enhanced inflammatory responses to endotoxin with increased disease incidence and severity during the periparturient period. However, the potential impact of oxylipids on leukocyte inflammatory marker expression during the periparturient period is unknown. The hypothesis of the Chapter 2 study was that a relationship exists between the profile of pro- and anti-inflammatory plasma oxylipids and the inflammatory phenotype of peripheral blood leukocytes during the periparturient period. Correlations were identified between concentrations of several plasma oxylipids, including some derived from linoleic acid, and expression of some proinflammatory markers by peripheral blood leukocytes. Previous reports of increased linoleic acid concentrations within mononuclear leukocytes during early lactation were confirmed. Human studies showed proinflammatory effects of linoleic acid in several cell types through oxylipid production. Early lactation monocytes were modeled in vitro to evaluate effects of increased linoleic acid concentrations on oxylipid production and inflammatory marker expression. The overall hypothesis of Chapter 3 studies was that increased monocyte linoleic acid concentrations enhance production of linoleic acid-derived oxylipids, induce a pro-inflammatory phenotype, and enhance inflammatory responses to endotoxin. Results showed increased production of several linoleic acid-derived oxylipids in primary bovine and murine RAW 264.7 monocytes with linoleic acid concentrations similar to early lactation cows. Increasing linoleic acid concentrations in monocytes did not impact pro- or anti-inflammatory marker expression and did not influence endotoxin-stimulated inflammatory responses. Future studies should evaluate the impact of individual oxylipids, produced by monocytes in response to increased linoleic acid concentration, on inflammatory marker expression.
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