Effects of ketones, acetate, butyrate, and glucose on bovine lymphocyte proliferation

Blood leukocytes from age-matched heifers were used to determine effects of ketones, acetate, butyrate, and glucose on in vitro lymphocyte proliferation. Lymphocytes stimulated with concanavalin A, phytohemagglutinin-P, or pokeweed mitogen were cultured in the presence or absence of beta-hydroxybutyrate, acetoacetate, acetone, acetate, butyrate, and glucose. Only supraphysiological levels of beta-hydroxybutyrate inhibited proliferation in cultures of mitogen-stimulated lymphocytes, whereas mixtures of beta-hydroxybutyrate and acetoacetate at levels seen in severe ketosis stimulated concanavalin A and phytohemagglutinin-P-driven proliferation. Because acetoacetate was a lithium salt, lithium chloride served as a negative control. Results suggest the enhanced proliferation by cultures containing lithium acetoacetate was due to lithium, not acetoacetate. Butyrate (at concentrations greater than seen in bovine plasma) and acetate at normal levels inhibited proliferation. Concanavalin A- and pokeweed-mitogen-driven proliferation was greater in cultures containing lower glucose levels, but acetate added to cultures containing low glucose inhibited concanavalin A-stimulated proliferation. Proliferation by pokeweed mitogen-stimulated cultures containing acetate, beta-hydroxybutyrate, and acetoacetate was suppressed at the lower concentrations of glucose tested. In conclusion, ketones, butyrate, and glucose at concentrations occurring in vivo had minimal effects on bovine lymphocyte proliferation in vitro. Levels of acetate associated with ketosis suppressed lymphocyte function and may alter immune responsiveness in vivo.