Effects of nonesterified fatty acids and beta-hydroxybutyrate on functions of mononuclear cells obtained from ewes

OBJECTIVE: To assess the effects of nonesterified fatty acids (NEFA) and beta-hydroxybutyrate (BHBA) on functions of mononuclear cells obtained from ewes. ANIMALS: 6 Sardinian ewes. PROCEDURE: Mononuclear cells were cultured with concentrations of NEFA (0, 15.6, 31.2, 62.5, 125, 250, 500, 1,000, or 2,000 micromol/L) and BHBA (0, 0.45, 0.9, 1.8, or 3.6 mmol/L). Concentrations of NEFA and BHBA were intended to mimic those of ketotic or healthy ewes, and NEFA and BHBA were tested alone and in combination. Synthesis of DNA was stimulated by use of concanavalin A (Con A) or pokeweed-mitogen (PWM). Secretion of IgM was stimulated by use of PWM. RESULTS: Synthesis of DNA stimulated by Con A and PWM was significantly inhibited by high concentrations of NEFA (> or = 250 micromol/L) or by a combination of high concentrations of NEFA (> or = 250 micromol/L) and all concentrations of BHBA (> or = 0.45 mmol/L). In contrast, DNA synthesis was not inhibited by low concentrations of NEFA (< or = 125 micromol/L) or by a combination of low concentrations of NEFA (< or = 125 micromol/L) and the lowest concentration of BHBA (0.45 mmol/L). Secretion of IgM was significantly inhibited by all concentrations of NEFA and by all combinations of NEFA and BHBA concentrations. When used alone, none of the concentrations of BHBA inhibited DNA synthesis or IgM secretion. CONCLUSIONS AND CLINICAL RELEVANCE: Reduced immunoresponsiveness during ketosis is likely to be associated with an increase in plasma concentration of NEFA and not with an increase in plasma concentration of BH BA.