DOI: 10.5061/dryad.72db024
title: Data from: Prophylactic digoxin treatment reduces IL-17 production in vivo in the neonatal calf and moderates RSV-associated disease

description: Respiratory syncytial virus (RSV) is a leading cause of morbidity and
 mortality in human infants. Bovine RSV infection of neonatal calves is
 pathologically and immunologically similar to RSV infection in infants,
 and is therefore a useful preclinical model for testing novel
 therapeutics. Treatment of severe RSV bronchiolitis relies on supportive
 care and may include use of bronchodilators and inhaled or systemic
 corticosteroids. Interleukin-17A (IL-17) is an inflammatory cytokine that
 plays an important role in neutrophil recruitment and activation. IL-17 is
 increased in children and rodents with severe RSV infection; and in calves
 with severe BRSV infection. It is currently unclear if IL-17 and Th17
 immunity is beneficial or detrimental to the host during RSV infection.
 Digoxin was recently identified to selectively inhibit IL-17 production by
 antagonizing its transcription factor, retinoid-related orphan receptor γ
 t (RORγt). Digoxin inhibits RORγt binding to IL-17 and Th17 associated
 genes, and suppresses IL-17 production in vitro in human and murine
 leukocytes and in vivo in rodent models of autoimmune disease. We
 demonstrate here that in vitro and in vivo digoxin treatment also inhibits
 IL-17 production by bovine leukocytes. To determine the role of IL-17 in
 primary RSV infection, calves were treated prophylactically with digoxin
 and infected with BRSV. Digoxin treated calves demonstrated reduced signs
 of clinical illness after BRSV infection, and reduced lung pathology
 compared to untreated control calves. Digoxin treatment did not adversely
 affect virus shedding or lung viral burden, but had a significant impact
 on pulmonary inflammatory cytokine expression on day 10 post infection.
 Together, our results suggest that exacerbated expression of IL-17 has a
 negative impact on RSV disease, and that development of specific therapies
 targeting Th17 immunity may be a promising strategy to improve disease
 outcome during severe RSV infection.
description: Data from Figure
 2PBMC
 cultured with or without digoxin, stimulated with BRSV or pokeweed
 mitogen. Data correspond to Figure 2 in manuscript.Figure
 2.xlsxData from Figure
 1Digoxin concentrations
 in serum. Data correspond to Figure 1 in manuscript.Figure 1_ digoxin in
 serum.xlsxData from Figure 3 -
 clinical scoresCalves were scored daily
 based on clinical signs (fever, cough, respiratory rate, etc.). Data
 correspond to Figure 3A in the manuscript.Figure 3A clinical
 scores.xlsxData from Figure
 4NS2
 copy numbers in the lungs of calves on day 10. Corresponds to Figure 4 in
 the manuscript.Figure 4 NS2 copy numbers in
 lung.xlsxData from Figure
 5RQ
 values from qPCR for various inflammatory cytokines expressed in lung
 tissue. Data correspond to Figure 5 in manuscript.Figure 5 qPCR
 data.xlsxData from Figure
 6Cytospins were done on
 bronchoalveolar lavage cells and differential counts were performed. Data
 correspond to Figure 6 in manuscript.Figure 6
 cytospins.xlsxData from Figure
 7ELISAs were performed to
 detect serum and nasal fluid antibodies, and cells were re stimulated and
 cytokines were measured by ELISA. Data correspond to Figure 7 in the
 manuscript.Figure
 7.xlsx