1,25-dihydroxyvitamin D-3 inhibits secretion of interferon-gamma by mitogen- and antigen-stimulated bovine mononuclear leukocytes

1,25-Dihydroxyvitamin D-3 (1,25(OH)(2)D-3), the biologically active metabolite of vitamin D, and Delta(22)-26-F-3-1,25-dihydroxyvitamin D-3 (Delta(22)-26-F-3-1,25(OH)(2)D-3), a synthetic analog with a high affinity for the vitamin D receptor, significantly inhibited interferon-gamma (IFN-gamma) secretion in 24- and 48-h cultures of pokeweed mitogen (PWM) and ovalbumin (OVA) stimulated peripheral blood mononuclear leukocyte (MNL) from adult, OVA-sensitized dairy cattle. Vitamin D-induced inhibition of IFN-gamma production was most pronounced in MNL cultures supplemented with 1,25(OH)(2)D-3 at 1.0 nM or more, a concentration equal to or exceeding that in plasma of cows with clinical hypocalcemia. Secreted IFN-gamma was undetectable in all resting MNL cultures, Ultra-low concentrations (0.0001, 0.001, and 0.01 nM) of 1,25(OH)(2)D-3 had no effect on IFN-gamma secretion by PWM-stimulated bovine MNL, unlike a previous study in other species demonstrating enhancement of IFN-gamma secretion at these concentrations, Preincubation of MNL with 1,25(OH2D3 (10 nM) in the absence of PWM for 1 h did not affect subsequent IFN-gamma secretion in control or 1,25(OH)(2)D-3-supplemented, 48-h MNL cultures indicating the sterol must be present at the time of MNL activation to effect secretion of IFN-gamma. Interferon-gamma secretion was inhibited in cultures supplemented with 1,25(OH)(2)D-3 at 0, 4, 8, 16, or 24 h into the 48-h incubation period. Overall, these data indicate that 1,25(OH)(2)D-3 inhibits IFN-gamma secretion by mitogen- and antigen-activated bovine MNL in vitro, and suggests that milk fever-related or therapeutically induced elevations of 1,25(OH)(2)D-3 in the daily cow may influence IFN-gamma secretion by in vivo activated leukocytes.