Effects of retinoic acid and 1,25-dihydroxyvitamin D3 on IFN-γ secretion by mononuclear leukocytes from nulliparous and postparturient dairy cattle

Individual and combined effects of several isomers of retinoic acid (RA) and 1,25-dihydroxyvitamin D-3 (1,25-(Oh)(2)D-3) on interferon-Psi (IFN-gamma) secretion by blood mononuclear leukocytes (MNL) from nulliparous and postparturient Holstein cattle were evaluated in vitro. In the first experiment, effects on incubation period ( 24 to 72 hours) and time of supplementation (0 to 32 hours) with all-trans, 9-cis, 13-cis-, and 9,13-dicis-RAs (0 to 100 nM) on IFN-gamma secretion by pokewood mitogen (PWM)-stimulated (0 and 10 mu g/ml) MNL from nulliparous cattle were evaluated. In the second experiment, MNL from postparturient cows (bled at 0,2,4 and 16 days postpartum) were stimulated with PWM (0 and 10 mu g/ml) in the presence of RA isomers (9-cis- or 9,13-dicis-RA; 0 to 100 nM), 1,25-(OH)(2)D-3 (0 to 100 nM), or with combinations of these metabolites. The results show that individual isomers of RA had no effect on IFN-gamma secretion by PWM-stimulated MNL from nulliparous or postparturient cows. Furthermore, 1,25-dihydroxyvitamin D-3 inhibited IFN-gamma secretion by MNL from nulliparous and postparturient dairy cows; however, the degree of inhibition was greater when 9-cis- and 9,13-dicis-RA were also present in the cultures. Finally mononuclear leukocytes from postparturient dairy cows produced substantially less IFN-gamma than did MNL from nulliparous cattle. It is concluded that retonoic acids individually did not affect the capacity of leukocytes from dairy cattle to secrete IFN-gamma. This result is in marked contrast to studies in monogastric species indicating that RAs inhibit IFN-gamma secretion by peripheral blood T cells. Inhibition of IFN-gamma secretion by 1,25-(OH)(2)-D-3 was potentiated by 9-cis- and 9,13-di-cis-retonoics acids, suggesting that an excess of dietary vitamins A and D may compromise further the naturally immunosuppressed postparturient dairy cow. Additional research is neccessary to determine if the combined effects of these metabolites on IFN-gamma secretion represent an increased susceptibility of the dairy cow to infectious diseases during the periparturient period. Lower secretion of IFN-gamma by MNL from postparturient dairy cows, relative to nulliparous cattle, suggests that recently-calved cows are naturally immunosupressed.