Submitted to: Veterinary Immunology and Immunopathology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: October 17, 1995
Publication Date: N/A
Interpretive Summary: Interferon-gamma (IFN-gamma), a protein produced by white blood cells (WBC), plays a key role in the body's defense against viruses, parasites, and in the prevention of cancer. Vitamin D known for its regulatory role in calcium metabolism recently has been found to affect many aspects of the immune system. Our results report that vitamin D [1,25(OH)2D3] inhibits IFN-gamma production by WBC from cattle. Inhibition was produced by concentrations of 1,25(OH)2D3 equal to those seen in the plasma of normal cows at calving time and in cows with the metabolic disease known as milk fever. These results suggest that the natural elevations in 1,25(OH)2D3 during the period before and after parturition or as a result of therapeutic intervention may affect the dairy cow's immune system and possibly its resistance to infectious diseases such as mastitis. Since the period immediately after calving is characterized by an increased incidence eof infectious diseases additional studies are needed to clarify the effect of vitamin D on the function of the immune system of the dairy cow.
Technical Abstract: 1,25-Dihydroxyvitamin D3 [1,25(OH)2D3], the biologically active metabolite of vitamin D, and delta22-26-F3-1,25-dihydroxyvitamin D3 [delta22-26-F3- 1,25(OH)2D3], 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)2D3 at greater than or equal to 1.0 nM, 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)2D3 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(OH)2D3 (10 nM) in the absence of PWM for 1 h did not affect subsequent IFN-gamma 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-gamma. Interferon-gamma 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-þ secretion by mitogen- and antigen-activated bovine MNL in vitro, and suggests that natural or therapeutically-induced elevations of 1,25(OH)2D3 in the dairy cow may modulate IFN-gamma secretion by in vivo-activated leukocytes.