G000701,25-Dihydroxyvitamin D[3] inhibits interferon-gamma (IFN-g) secretion by lectin stimulated mononuclear leukocytes (PBMC) from dairy cattle
B. N Ametaj (1), B. J. Nonnecke (1), T. A. Reinhardt (1) and D. C. Beitz (2)
(1) National Animal Disease Center-USDA-ARS
(2) Iowa State University, Ames IA, 50010
Abstract:
1,25-Dihydroxyvitamin D3 (1,25-(OH)[2]D[3]), the most potent, biological metabolite of vitamin D, modulates the proliferation and differentiation of bovine CD4^+ and CD8^+ PBMC in vitro. The effect of 1,25-(OH)[2]D[3] and two synthetic analogues, 22-26-F[3]-1,25-(OH)[2]D[3] and 1,25,28-(OH)[3]D[2] on IFN-gamma secretion by PBMC from ovalbumin (OVA)-sensitized adult dairy cattle were evaluated. Mononuclear leukocyte cultures were unstimulated or stimulated with pokeweed mitogen (5 and 10 microgram/ml); OVA (16 and 32 microgram/ml) or lipopolysaccharide (LPS, 10 microgram/ml). Vitamin D concentrations in cultures were 0, 10^-10, 10^-9, 10^-8 moles/L. Culture supernatants were harvested at 24 and 48h and analyzed for IFN-g using an IFN-g-capture ELISA. Interferon-g secretion by resting and LPS-stimulated cultures was undetectable in control and vitamin D-supplemented cultures. 1,25-(OH)[2]D[3], at 10-9 and 10-8 moles/L, inhibited (P<.05) secretion by PWM-stimulated cells; however, the synthetic analogue, 22-26-F[3]-1,25-(OH)[2]D[3] at 10^-10 to 10^-8 moles/L inhibited (P<.001) IFN-g secretion by PWM-stimulated cells under all culture conditions. 1,25,28-(OH)[3]D[2] at 10^-10 to 10^-8 moles/L had no effect (P>.05) under the same culture conditions. Interferon secretion in OVA-stimulated was less than in PWM-stimulated cultures and effects of all the metabolites were much less pronounced in these cultures than in PWM-stimulated cultures. Overall, these result indicate that 1,25-(OH)[2]D[3] and 22-26-F3-1,25-(OH)[2]D[3] are potent inhibitors of IFN-g secretion by in vitro activated bovine PBMC. These results and previous research indicating this hormone enhances immunoglobulin secretion, possibly through its effect on T cell populations, suggests that this hormone may promote the development humoral rather than cellular immune responses in dairy cattle.
Comments:
Address questions and comments about this abstract to Brian J. Nonnecke ( bnonneck@nadc.ars.usda.gov).
Previously presented at American Dairy Science Association Meeting on June 1996.