Differential Expression of Cytokines in Response to Respiratory Syncytial Virus Infection of Calves with High or Low Circulating 25-Hydroxyvitamin D3

Abstract

Deficiency of serum levels of 25-hydroxyvitamin D3 has been related to increased risk of lower respiratory tract infections in children. Respiratory syncytial virus (RSV) is a leading cause of low respiratory tract infections 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-γ) 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 and deficient vitamin D levels.

Vitamin D [1,25(OH)2D3] Differentially Regulates Human Innate Cytokine Responses to Bacterial versus Viral Pattern Recognition Receptor Stimuli

“…This suggests that the commonly cited conclusion that vitamin D is inherently anti-inflammatory offers an oversimplification of its multiple effects on the human immune system. Indeed, the complexity of vitamin D biology in different species, tissues and stimuli is increasingly evident (36,37).…”

Acute phase response elicited by experimental bovine diarrhea virus (BVDV) infection is associated with decreased vitamin D and E status of vitamin-replete preruminant calves

“…The authors propose that the positive effects of vitamin D treatment are likely due to its enhancement of the innate immune system in the vitamin D-deficient milk compartment of the mammary gland. Sacco et al (2012) examined the effects of vitamin D status on lung pathology and cytokine response of the preruminant calf experimentally infected with bovine respiratory syncytial virus (BRSV). Although the extent of lung pathology was comparable in calves with low and high vitamin D status, this study was the first to show that BRSV infection activates the vitamin D intracrine signaling pathway in the inflamed lung of the preruminant calf.…”

Comparison of Zinc,Vitamin A &D Serum Levels Between Children With Respiratory Tract Infection And Healthy Individuals in two Iranian Referral Hospitals

“…An animal trial performed by Sacco was not able to reveal the relation between RSV infection and vitamin Dserum level (30).…”