Effect of different fatty acids on the proliferation and cytokine production of dairy cow peripheral blood mononuclear cells

Abstract

During the transition period, dairy cows often experience negative energy balance, which induces metabolic and immunological disturbances. Our previous work has shown a relationship between the inhibition of immune functions and increased blood nonesterified fatty acid (NEFA) levels. In this study, we evaluated the effect of 11 fatty acids (palmitoleic, myristic, palmitic, stearic, oleic, linoleic, docosahexaenoic, conjugated linoleic, lauric, eicosapentaenoic, and linolenic acids) as well as a mix that represented the NEFA profile observed during the transition period at different concentrations (0, 50, 100, and 250 µM) on proliferation and cytokines secretion of lymphocytes. To assess lymphoproliferation, peripheral blood mononuclear cell (PBMC) from 5 healthy cows (166-189 d in milk) were isolated, stimulated with the mitogenic lectin concanavalin A (ConA), incubated for 72 h with or without fatty acids, and subjected to flow cytometry analysis. Our results showed that all fatty acids, except lauric acid, significantly reduced proliferation of PBMC in a dose-dependent manner. The most detrimental effect was observed with conjugated linoleic and stearic acids, where proliferation of PBMC was already inhibited at the lowest dose (50 µM). For cytokine secretion, we found that levels of IL-4 in culture supernatant of ConA-stimulated PBMC were reduced after a 24-h exposure to the lowest dose (50 µM) of oleic and palmitoleic acids. A dose of 100 µM of eicosapentaenoic acid, NEFA mixture, and myristic acid was necessary to observe a reduction in IL-4 levels. The PBMC also showed a decrease in the secretion of IFN-γ in response to lauric, linolenic, palmitoleic, and stearic acids at 50 µM and myristic acid at 100 µM. Overall, polyunsaturated fatty acids were more potent inhibitors of cytokine secretions than saturated fatty acids. In addition, we detected an inverse relationship between the melting points of fatty acids and their ability to inhibit IL-4 and IFN-γ secretions, as evidenced by greater inhibition with low-melting point fatty acids. Overall, our study confirmed that NEFA have a negative effect on some lymphocyte functions, and that their inhibitory effect on cytokine secretions increases with the degree of unsaturation.