In vitro effects of 1,25-dihydroxyvitamin D3 on interferon-γ and tumor necrosis factor-α secretion by blood leukocytes from young and adult cattle vaccinated with Mycobocterium bovis BCG

Interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha) are critical in the development of an effective immune response. Vitamin D, essential in short-term calcium homeostasis and recently shown to modulate proliferation and function of blood mononuclear cells from adult dairy cattle, may be an effective modulator of the calf's immune system. Effects of antigen sensitization and 1,25-dihydroxyvitamin D-3 [1,25-(OH)(2)D-3] on cytokine secretion by cells from calves vaccinated with Bacille Calmette-Guerin (BCG) were examined. One-week-old dairy calves (n = 6) and yearling heifers (n = 4) were vaccinated concurrently with BCG and boosted six weeks later. Ten weeks after primary vaccination, cells from vaccinated calves and adults, and nonvaccinated, age-matched calves (n = 4) were evaluated in vitro for their capacity to produce IFN-gamma and TNF-alpha. Cells were stimulated with pokeweed mitogen (PWM) or recall antigen [Mycobacterium bovis-derived purified protein derivative (PPD)] in the presence of 0, 0.1, 1.0, and 10nM of 1,25-(OH)(2)D-3 for 20, 44, and 68 hours, respectively. IFN-gamma and TNF-alpha concentrations in culture supernatents harvested at these times were quantified by enzyme-linked immunosorbent assay (ELISA). PPD-induced IFN-gamma and TNF-alpha responses of cells from vaccinated calves and adults were greater then responses of autologous unstimulated cells. In contrast, PPD-specific responses of calf and adult cells collected immediately before primary vaccination were substantially lower and comparable to responses of nonvaccinated calves; however, responses of vaccinated calves were more vigorous than corresponding responses of vaccinated adults. Incubation period also influenced the magnitude of both IFN-gamma and TNF-alpha responses in PPD- and PWM-stimulated cultures. Effects of 1,25-(OH)(2)D-3 on antigen-induced secretion of IFN-gamma and TNF-alpha secretion by bovine leukocytes and suggest that 1,25-(OH)(2)D-3 can alter secretion of both cytokines under specific conditions of culture.