1,25-Dihydroxyvitamin D3 inhibits secretion of interferon-γ by mitogen- and antigen-stimulated bovine mononuclear leukocytes

1,25-Dihydroxyvitamin D3 (1,25(OH)2D3), the biologically active metabolite of vitamin D, and Δ22-26-F3-1,25-dihydroxyvitamin D3 (Δ22-26-F3-1,25(OH)2D3), a synthetic analog with a high affinity for the vitamin D receptor, significantly inhibited interferon-γ (IFN-γ) 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-γ production was most pronounced in MNL cultures supplemented with 1,25(OH)2D3 at 1.0 nM or more, a concentration equal to or exceeding that in plasma of cows with clinical hypocalcemia. Secreted IFN-γ was undetectable in all resting MNL cultures. Ultra-low concentrations (0.0001, 0.001, and 0.01 nM) of 1,25(OH)2D3 had no effect on IFN-γ secretion by PWM-stimulated bovine MNL, unlike a previous study in other species demonstrating enhancement of IFN-γ secretion at these concentration. Preincubation of MNL with 1,25(OH2D3 (10 nM) in the absence of PWM for 1 h did not affect subsequent IFN-γ secretion in control or 1,25(OH)2D3-supplemented, 48-h MNL cultures indicating the sterol must be present at the time of MNL activation to effect secretion of IFN-γ. Interferon-γ secretion was inhibited in cultures supplemented with 1,25(OH)2D3 at 0, 4, 8, 16, or 24 h into the 48-h incubation period. Overall, these data indicate that 1,25(OH)2D3 inhibits IFN-γ secretion by mitogen- and antigen-activated bovine MNL in vitro, and suggests that milk fever-related or therapeutically induced elevations of 1,25(OH)2D3 in the dairy cow may influence IFN-γ secretion by in vivo activated leukocytes.