Abstract
Low-dose hydrocortisone (LDHC) therapy modulates inflammatory responses in adults and improves outcomes in some septic adults and neonates, but its immunologic effects have not been evaluated in neonates. The objective of this study was to evaluate effects of LDHC therapy on ex vivo immune function in neonatal horses (foals). We hypothesized that LDHC treatment would dampen proinflammatory responses without impairing neutrophil function. Hydrocortisone (1.3 mg/kg/d i.v.) was administered to foals in a tapering 3.5 d course. Peripheral blood leukocytes were collected from foals before, during, and after hydrocortisone treatment. A separate group of age-matched untreated foals served as controls. Endotoxin-induced peripheral blood mononuclear cell gene expression of inflammatory cytokines was measured by real-time quantitative RT-PCR. Neutrophils were incubated with labeled, killed Staphylococcus aureus or Escherichia coli for assessment of phagocytosis, and with phorbol myristate acetate, zymosan, or endotoxin for measurement of reactive oxygen species (ROS) production. Neutrophil phagocytosis and ROS production were similar in both groups. Foals receiving hydrocortisone had significantly decreased endotoxin-induced expression of TNF-α, IL-6, IL-8, and IL-1β. These data suggest that this LDHC treatment regimen ameliorates endotoxin-induced proinflammatory cytokine expression in neonatal foals without impairing innate immune responses needed to combat bacterial infection.
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Abbreviations
- CIRCI:
-
critical illness-related corticosteroid insufficiency
- HPA:
-
hypothalamic-pituitary-adrenal
- LDHC:
-
low-dose hydrocortisone
- PBMC:
-
peripheral blood mononuclear cell
- PMA:
-
phorbol myristate acetate
- RAI:
-
relative adrenal insufficiency
- ROS:
-
reactive oxygen species
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Acknowledgements
We thank Lorelei Jones, Kari Anderson, Dr. Gary Heusner, Dr. Greg Queen, and the students who assisted with sampling; Londa Berghaus, Shay Bush, Kate Hurley, Natalie Norton, Denise Pope, and Caroline Salter for technical assistance; and Dr. Roy Berghaus for statistical consultation.
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Supported by grants from the National Institutes of Health (GM086003), the Grayson Jockey Club Research Foundation, and the American Quarter Horse Foundation.
Portions of this work were presented in abstract form at the American College of Veterinary Internal Medicine Annual Forum, Anaheim, California, June 9–12, 2010.
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Hart, K., Barton, M., Vandenplas, M. et al. Effects of Low-Dose Hydrocortisone Therapy on Immune Function in Neonatal Horses. Pediatr Res 70, 72–77 (2011). https://doi.org/10.1203/PDR.0b013e31821b502b
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DOI: https://doi.org/10.1203/PDR.0b013e31821b502b
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