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Title:   Author  item
                                            Sacco, Randyitem
                                            Nonnecke, Brianitem
                                            Palmer, Mitchellitem
                                            Waters, Wadeitem
                                            Lippolis, Johnitem
                                            Reinhardt, Timothy
  Submitted to: PLOS ONE
                                    Publication Type: Peer Reviewed Journal
                                    Publication Acceptance Date: 2/9/2012
                                    Publication  Date: 3/8/2012
                                    Citation: Sacco, R.E., Nonnecke, B.J., Palmer, M.V., Waters, W.R., Lippolis, J.D., Reinhardt, T.A. 2012. Differential expression of cytokines in response to respiratory syncytial virus infection of calves with high or low circulating 25-hydroxyvitamin D3. PLoS One. 7(3):e33074. Available: http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0033074.Interpretive Summary: There is speculation that vitamin D supplementation could be effective against infections. In this study, two groups of calves were fed milk replacers that had different amounts of vitamin D. One group of calves was fed a milk replacer with high vitamin D and the other group was fed a milk replacer with low vitamin D. These two groups of calves were then infected with bovine respiratory syncytial virus (RSV) for 7 days. There were no observed differences in the response to bovine RSV between the two groups of calves. There is a need for longer-term studies on the effects of vitamin D on the response to RSV.
                                Technical Abstract: Deficiency of serum levels of 25-hydroxyvitamin D3 has been related to increased risk of lower respiratory tract infections (LRTI) in children. Respiratory syncytial virus (RSV) is the leading cause of LRTI in infants and young children. The neonatal calf model of RSV infection shares many features in common with RSV infection in infants and children. In the present study, we hypothesized that calves with low circulating levels of 25-hydroxyvitamin D3 (25(OH)D3) would be more susceptible to RSV infection than calves with high circulating levels of 25(OH)D3. Calves were fed milk replacer diets with different levels of vitamin D for a 10-wk period to establish two treatment groups, one with high (177 ng/ml) and one with low (32.5 ng/ml) circulating 25(OH)D3. Animals were experimentally infected via aerosol challenge with RSV. Data on circulating 25(OH)D3 levels showed that high and low concentrations of 25(OH)D3 were maintained during infection. At necropsy, lung lesions due to RSV were similar in the two vitamin D treatment groups. We show for the first time that RSV infection activates the vitamin D intracrine pathway in the inflamed lung. Importantly, however, we observed that cytokines frequently inhibited by this pathway in vitro are, in fact, either significantly upregulated (IL-12p40) or unaffected (IFN-gamma) in the lungs of RSV-infected calves with high circulating levels of 25(OH)D3. Our data indicate that while vitamin D does have an immunomodulatory role during RSV infection, there was no significant impact on pathogenesis during the early phases of RSV infection. Further examination of the potential effects of vitamin D status on RSV disease resolution will require longer-term studies with immunologically sufficient or deficient vitamin D levels.


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