Submitted to: International Journal for Vitamin and Nutrition Research
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 3/10/2003
Publication Date: 7/20/2003
Citation: Nonnecke, B.J., Waters, W.R., Foote, M.R., Fowler, M.A., Horst, R.L., Miller, B.L. 2003. In vitro effects of 1,25-Dihydroxyvitamin D3 on interferon-gamma and tumor necrosis factor-alpha secretion by blood leukocytes from young and adult cattle vaccinated with Mycobacterium bovis BCG. International Journal for Vitamin and Nutrition Research. 73(4):235-244. Interpretive Summary: Vaccination of the neonatal calf shortly after birth is necessary to protect it against pathogens that pose significant disease risk during its maturation to adulthood. Protection afforded by early immunization is especially critical to the calf given the number and diversity of potential pathogens in its environment. A general assumption is that the immune system of the newborn calf is developmentally immature rendering it less responsive to immunization and more susceptible to infectious disease. IFN-gamma and TNF-alpha are proteins produced by immune cells that are critical in the development of an effective immune response to pathogens. 1,25-Dihydroxyvitamin D3, the biologically active form of vitamin D, is essential in regulating calcium levels in the body and has recently been shown to modulate the function of the immune system of adult dairy cattle. The present study evaluated the effects of 1,25-dihydroxyvitamin D3 on the production of IFN-gamma and TNF-alpha by immune cells of young calves and adult cattle vaccinated with Mycobacterium bovis BCG, a non-disease producing bacterium related to the bacterium that causes tuberculosis in cattle. Surprisingly, the IFN-gamma and TNF-alpha responses of vaccinated calves to subsequent exposure to the organism were comparable to those of adult cattle. These results suggest that the calf vaccinated within a week of birth is capable of mounting an effective response to this bacterium. It is likely that these robust responses to the organism would afford protection from exposure to a variety of organisms. In addition, IFN-gamma and TNF-alpha responses of calves and adult cattle were affected influenced by vitamin D, suggesting this vitamin may be an effective modulator of the immune system of young and adult dairy cattle.
Technical Abstract: IFN-gamma and 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 PBMC from adult cattle, may be an effective modulator of the calf's immune system. Effects of antigen sensitization and 1,25-dihydroxyvitamin D3 [1,25(OH2)D3] on IFN-gamma and TNF-alpha secretion by blood mononuclear leukocytes from calves vaccinated with BCG were examined. One-wk-old dairy calves (n=6) and yearling heifers (n=4) were vaccinated concurrently with BCG and boosted 6 wk 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. Cultures were unstimulated or stimulated with PWM and antigen (Mycobacterium bovis PPD) in the presence of 0, 0.1, 1.0, and 10 mM of 1,25(OH)2D3 for 20, 44, and 68 h. IFN-gamma and TNF-alpha concentrations in culture supernatants harvested at these times were quantified by ELISA. PPD-induced IFN-gamma and TNF-alpha responses of cells from vaccinated calves and adults were greater than responses of autologous unstimulated cells as well as the responses of PPD-stimulated cells from nonvaccinated calves. PPD-induced IFN-gamma and TNF-alpha responses of cells from vaccinated calves were greater than responses of cells from vaccinated adults. Relative to calf cells, adult cells produced more IFN-gamma and comparable amounts of TNF-alpha when stimulated with PWM. Duration of the incubation period also influenced the magnitude of both IFN-gamma and TNF-alpha responses in PPD- and PWM-stimulated cultures. Secretion of TNF-alpha was maximal from 20-44 h, whereas IFN-gamma secretion was maximal from 44 to 68 h. Effects of 1,25(OH)2D3 on antigen-induced IFN-gamma and TNF-alpha were marginal. Only IFN-gamma responses of PBMC from vaccinated adults were affected by 1,25(OH)2D3. In PWM-stimulated cultures of calf and adult leukocytes, the sterol caused a concentration-dependent decrease in IFN-gamma responses and an increase in TNF-alpha responses. Overall, these results indicate that animal maturity (i.e. age) and antigenic experience affect IFN-gamma and TNF-alpha secretion by bovine PBMC and suggest that 1,25(OH)2D3 can alter secretion of both cytokines under specific conditions of culture.