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Equine veterinary journal2025; 58(2); 359-371; doi: 10.1111/evj.70093

The potential value of cytokine, cortisol and vitamin D profiles in foals from birth to weaning for respiratory disease prediction on a farm endemic for Rhodococcus equi pneumonia.

Abstract: Rhodococcus equi causes pneumonia in young foals, but disease susceptibility and severity vary. Cortisol and vitamin D modulate immune responses and cytokine production during bacterial infection, and altered concentrations are associated with sepsis in neonatal foals. We hypothesised an age and disease effect on circulating steroid hormone concentrations in foals, and that differences in cytokines and steroid hormone concentrations would predict disease severity in pneumonic foals. Objective: To investigate circulating concentrations of various cytokines, cortisol and vitamin D as predictors of individual disease severity in R. equi foals. Methods: Prospective cohort. Methods: Blood samples were collected from 200 initially healthy foals on a pneumonia-endemic breeding farm after birth and at 1, 2, 4, 8, 12 and 20 weeks of age. Health status was tracked weekly. At weaning (20 weeks), foals were divided into three health groups: (1) foals that remained healthy, (2) foals that developed subclinical, self-resolving pneumonia and (3) foals that developed clinically apparent pneumonia necessitating antimicrobial treatment. Foals were randomly selected (n = 30/group) for cortisol, vitamin D and cytokine (TNFα, IL-4, IL-10, IL-17 and interferon-gamma [IFN-γ]) analysis using validated assays. Results: We observed disease-associated differences for IFN-γ at 4 weeks (χ = 13.91; df = 2; p = 0.001) and 20 weeks (χ = 10.0; df = 2; p = 0.007) and age-associated differences for cortisol, vitamin D and other cytokines (p < 0.001). Conclusions: Causative agent not identified, frequency and timing of sample collection may have impacted results, and systemic cytokine concentrations may not accurately reflect cytokine availability and activity at the tissue level. Conclusions: Periodic measurement of circulating steroid hormones and cytokines from birth to weaning was not predictive of pneumonia susceptibility and severity in foals on a farm with endemic pneumonia. Disease-associated IFN-γ differences warrant further investigation.
© 2025 The Author(s). Equine Veterinary Journal published by John Wiley & Sons Ltd on behalf of EVJ Ltd.
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Publication Date: 2025-09-09 PubMed ID: 40923138PubMed Central: PMC12892387DOI: 10.1111/evj.70093Google Scholar: Lookup
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Summary

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Overview

  • This study investigated whether blood levels of cytokines, cortisol, and vitamin D from birth to weaning could predict respiratory disease severity caused by Rhodococcus equi pneumonia in foals on a farm where the disease is common.
  • The researchers found that while some immune markers varied with age and disease state, routine measurement of these markers was not effective at predicting which foals would develop pneumonia or how severe it would be.

Background and Purpose

  • Rhodococcus equi pneumonia: A bacterial infection that causes lung disease primarily in young foals, but susceptibility and disease severity differ among individuals.
  • Immune modulation by cortisol and vitamin D: Both hormones influence immune responses and the production of cytokines—signaling proteins involved in inflammation and infection control.
  • Previous findings: Altered levels of cortisol and vitamin D have been linked to sepsis (blood infection) in newborn foals.
  • Study hypothesis: The authors proposed that circulating concentrations of steroid hormones (like cortisol and vitamin D) and cytokines would differ depending on age and disease status, and these differences might predict the severity of pneumonia in infected foals.

Study Design and Methods

  • Type of study: Prospective cohort study conducted on a breeding farm with endemic R. equi pneumonia.
  • Subjects: 200 foals initially healthy at birth.
  • Sampling timeline: Blood samples were collected at birth and at 1, 2, 4, 8, 12, and 20 weeks of age.
  • Health monitoring: Foals were monitored weekly to track development of pneumonia.
  • Grouping by health outcome at 20 weeks (weaning):
    • Group 1: Foals that remained healthy.
    • Group 2: Foals that developed subclinical pneumonia that resolved without treatment.
    • Group 3: Foals that developed clinically apparent pneumonia requiring antimicrobial treatment.
  • Sample selection for detailed analysis: 30 foals randomly chosen from each group for measurement of cortisol, vitamin D, and cytokines.
  • Analytes measured: Cytokines included TNFα, IL-4, IL-10, IL-17, and interferon-gamma (IFN-γ) using validated assays.

Key Results

  • IFN-γ differences: Significant differences in interferon-gamma levels between health groups were detected at 4 weeks (p = 0.001) and at 20 weeks (p = 0.007), suggesting some association of this cytokine with disease status.
  • Age-related changes: Cortisol, vitamin D, and other cytokines showed significant variation depending on age (p < 0.001), reflecting normal developmental immune changes.
  • No predictive value: Regular measurements of cytokines, cortisol, and vitamin D between birth and weaning did not consistently predict which foals would develop pneumonia or the severity of disease.

Interpretations and Limitations

  • Unidentified causative agent impact: Although R. equi is the suspected pathogen, specific confirmation was limited.
  • Sampling limitations: The frequency and timing of blood sampling may not have captured the critical windows when immune changes occur.
  • Systemic versus local immune response: Blood cytokine levels might not accurately reflect cytokine activity within lung tissues where infection occurs.
  • Implications for practice: Routine blood monitoring of these immune markers is not helpful alone to predict pneumonia risk or severity in foals.

Conclusions and Future Directions

  • Regular measurement of circulating cytokines, cortisol, and vitamin D from birth to weaning did not effectively predict pneumonia susceptibility or severity in foals on an endemic farm.
  • The observed disease-associated differences in IFN-γ levels deserve further research to understand their role in immune defense or disease progression.
  • Future studies should consider more frequent or tissue-specific sampling and investigate additional immune parameters to improve prediction and understanding of foal pneumonia.

Cite This Article

APA
Berghaus LJ, Venner M, Helbig H, Hildebrandt D, Hart K. (2025). The potential value of cytokine, cortisol and vitamin D profiles in foals from birth to weaning for respiratory disease prediction on a farm endemic for Rhodococcus equi pneumonia. Equine Vet J, 58(2), 359-371. https://doi.org/10.1111/evj.70093

Publication

Equine veterinary journal
ISSN: 2042-3306
NlmUniqueID: 0173320
Country: United States
Language: English
Volume: 58
Issue: 2
Pages: 359-371

Researcher Affiliations

Berghaus, Londa J
  • Large Animal Medicine, University of Georgia, Athens, Georgia, USA.
Venner, Monica
  • Equine Clinic, Destedt, Germany.
Helbig, Hannah
  • Clinic for Horses, University of Veterinary Medicine Hanover, Foundation, Hanover, Germany.
Hildebrandt, Dorothea
  • Clinic for Horses, University of Veterinary Medicine Hanover, Foundation, Hanover, Germany.
Hart, Kelsey
  • Large Animal Medicine, University of Georgia, Athens, Georgia, USA.

MeSH Terms

  • Animals
  • Horses
  • Rhodococcus equi
  • Cytokines / blood
  • Cytokines / metabolism
  • Horse Diseases / microbiology
  • Horse Diseases / blood
  • Vitamin D / blood
  • Hydrocortisone / blood
  • Actinomycetales Infections / veterinary
  • Actinomycetales Infections / blood
  • Actinomycetales Infections / microbiology
  • Animals, Newborn
  • Female
  • Male
  • Pneumonia, Bacterial / veterinary
  • Pneumonia, Bacterial / blood
  • Pneumonia, Bacterial / microbiology
  • Weaning

Grant Funding

  • University of Georgia - Marguerite Thomas Hodgson Chair Equine Studies
  • Grayson Jockey Club Research Foundation

Conflict of Interest Statement

The authors declare no conflicts of interests.

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