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Home / Equine Research Bank / Equine Vet J / The potential value of cytokine, cortisol and vitamin D prof...
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.

References

This article includes 61 references
  1. Giguère S, Cohen ND, Keith Chaffin M, Hines SA, Hondalus MK, Prescott JF. Rhodococcus equi: clinical manifestations, virulence, and immunity.. J Vet Intern Med 2011;25(6):1221–1230.
    pubmed: 22092609
  2. Venner M, Rödiger A, Laemmer M, Giguère S. Failure of antimicrobial therapy to accelerate spontaneous healing of subclinical pulmonary abscesses on a farm with endemic infections caused by. Vet J 2012;192(3):293–298.
    pubmed: 21924651
  3. Ainsworth DM, Eicker SW, Yeagar AE, Sweeney CR, Viel L, Tesarowski D. Associations between physical examination, laboratory, and radiographic findings and outcome and subsequent racing performance of foals with infection: 115 cases (1984–1992).. J Am Vet Med Assoc 1998;213(4):510–515.
    pubmed: 9713534
  4. Giguère S, Cohen ND, Chaffin MK, Slovis NM, Hondalus MK, Hines SA. Diagnosis, treatment, control, and prevention of infections caused by in foals.. J Vet Intern Med 2011;25(6):1209–1220.
    pubmed: 22092608
  5. Adkins B, Leclerc C, Marshall‐Clarke S. Neonatal adaptive immunity comes of age.. Nat Rev Immunol 2004;4(7):553–564.
    pubmed: 15229474
  6. Murphy K et al. Janeway's immunobiology. 8th ed. New York, NY: Garland Science; 2012. p. xix, 868.
  7. Kanaly ST, Hines SA, Palmer GH. Cytokine modulation alters pulmonary clearance of and development of granulomatous pneumonia.. Infect Immun 1995;63(8):3037–3041.
    pmc: PMC173413pubmed: 7622227
  8. Nordmann P, Ronco E, Guenounou M. Involvement of interferon‐gamma and tumor necrosis factor‐alpha in host defense against. J Infect Dis 1993;167(6):1456–1459.
    pubmed: 8501339
  9. Breathnach CC, Sturgill‐Wright T, Stiltner JL, Adams AA, Lunn DP, Horohov DW. Foals are interferon gamma‐deficient at birth.. Vet Immunol Immunopathol 2006;112(3–4):199–209.
    pubmed: 16621024
  10. Boyd NK, Cohen ND, Lim WS, Martens RJ, Chaffin MK, Ball JM. Temporal changes in cytokine expression of foals during the first month of life.. Vet Immunol Immunopathol 2003;92(1–2):75–85.
    pubmed: 12628765
  11. Bordin AI, Huber L, Sanz MG, Cohen ND. foal pneumonia: update on epidemiology, immunity, treatment and prevention.. Equine Vet J 2022;54(3):481–494.
    pubmed: 35188690
  12. Berghaus LJ, Giguère S, Bordin AI, Cohen ND. Effects of priming with cytokines on intracellular survival and replication of in equine macrophages.. Cytokine 2018;102:7–11.
    pubmed: 29245049
  13. Harris SP, Hines MT, Mealey RH, Alperin DC, Hines SA. Early development of cytotoxic T lymphocytes in neonatal foals following oral inoculation with. Vet Immunol Immunopathol 2011;141(3–4):312–316.
    pmc: PMC3345954pubmed: 21481947
  14. Bordin AI, Cohen ND, Giguère S, Bray JM, Berghaus LJ, Scott B. Host‐directed therapy in foals can enhance functional innate immunity and reduce severity of pneumonia.. Sci Rep 2021;11(1):2483.
    pmc: PMC7844249pubmed: 33510265
  15. Giguère S, Wilkie BN, Prescott JF. Modulation of cytokine response of pneumonic foals by virulent. Infect Immun 1999;67(10):5041–5047.
    pmc: PMC96851pubmed: 10496876
  16. nGiguère S, Prescott JF. Cytokine induction in murine macrophages infected with virulent and avirulent n. Infect Immun. 1998;66(5):1848–1854.n
    pmc: PMC108134pubmed: 9573060
  17. nBerghaus LJ, Giguère S, Sturgill TL. Effects of age and macrophage lineage on intracellular survival and cytokine induction after infection with n. Vet Immunol Immunopathol. 2014;160(1–2):41–50.n
    pubmed: 24736188
  18. Ikuta K, Ejima A, Abe S, Shimba A. Control of immunity and allergy by steroid hormones. Allergol Int. 2022;71(4):432–436.
    pubmed: 35973911
  19. Hart KA, Heusner GL, Norton NA, Barton MH. Hypothalamic‐pituitary‐adrenal axis assessment in healthy term neonatal foals utilizing a paired low dose/high dose ACTH stimulation test. J Vet Intern Med. 2009;23(2):344–351.
    pubmed: 19192152
  20. Pozza ME, Kaewsakhorn T, Trinarong C, Inpanbutr N, Toribio RE. Serum vitamin D, calcium, and phosphorus concentrations in ponies, horses and foals from the United States and Thailand. Vet J. 2014;199(3):451–456.
    pubmed: 24524849
  21. Hart KA, Barton MH, Ferguson DC, Berghaus R, Slovis NM, Heusner GL, et al. Serum free cortisol fraction in healthy and septic neonatal foals. J Vet Intern Med. 2011;25(2):345–355.
    pubmed: 21281351
  22. Kamr AM, Dembek KA, Reed SM, Slovis NM, Zaghawa AA, Rosol TJ, et al. Vitamin D metabolites and their association with calcium, phosphorus, and PTH concentrations, severity of illness, and mortality in hospitalized equine neonates. PLoS One. 2015;10(6):e0127684.
    pmc: PMC4457534pubmed: 26046642
  23. Hart KA, Slovis NM, Barton MH. Hypothalamic‐pituitary‐adrenal axis dysfunction in hospitalized neonatal foals. J Vet Intern Med. 2009;23(4):901–912.
    pubmed: 19496914
  24. nArnold‐Lehna D, Venner M, Berghaus LJ, Berghaus R, Giguère S. Changing policy to treat foals with pneumonia in the later course of disease decreases antimicrobial usage without increasing mortality rate. Equine Vet J. 2020;52(4):531–537.n
    pubmed: 31808183
  25. Venner M, Kerth R, Klug E. Evaluation of tulathromycin in the treatment of pulmonary abscesses in foals. Vet J. 2007;174(2):418–421.
    pubmed: 17045497
  26. Venner M, Reinhold B, Beyerbach M, Feige K. Efficacy of azithromycin in preventing pulmonary abscesses in foals. Vet J. 2009;179(2):301–303.
    pubmed: 18023599
  27. nVenner M, Astheimer K, Lämmer M, Giguère S. Efficacy of mass antimicrobial treatment of foals with subclinical pulmonary abscesses associated with n. J Vet Intern Med. 2013;27(1):171–176.n
    pubmed: 23278131
  28. nHines SA, Stone DM, Hines MT, Alperin DC, Knowles DP, Norton LK, et al. Clearance of virulent but not avirulent from the lungs of adult horses is associated with intracytoplasmic gamma interferon production by CD4+ and CD8+ T lymphocytes. Clin Diagn Lab Immunol. 2003;10(2):208–215.n
    pmc: PMC150533pubmed: 12626444
  29. Wagner B, Freer H. Development of a bead‐based multiplex assay for simultaneous quantification of cytokines in horses. Vet Immunol Immunopathol. 2009;127(3–4):242–248.
    pubmed: 19027964
  30. nBerghaus LJ, Cathcart J, Berghaus RD, Ryan C, Toribio RE, Hart KA. The impact of age on vitamin D receptor expression, vitamin D metabolism and cytokine production in ex vivo infection of equine alveolar macrophages. Vet Immunol Immunopathol. 2024;268:110707.n
    pubmed: 38181474
  31. Burton AB, Wagner B, Erb HN, Ainsworth DM. Serum interleukin‐6 (IL‐6) and IL‐10 concentrations in normal and septic neonatal foals. Vet Immunol Immunopathol. 2009;132(2–4):122–128.
    pubmed: 19501415
  32. Naskou MC, Norton NA, Copland IB, Galipeau J, Peroni JF. Innate immune responses of equine monocytes cultured in equine platelet lysate. Vet Immunol Immunopathol. 2018;195:65–71.
    pubmed: 29249319
  33. Lopez BS, Hurley DJ, Giancola S, Giguère S, Felippe MJB, Hart KA. The effect of age on foal monocyte‐derived dendritic cell (MoDC) maturation and function after exposure to killed bacteria. Vet Immunol Immunopathol. 2019;210:38–45.
    pubmed: 30947978
  34. Reimers TJ, Salerno VJ, Lamb SV. Validation and application of solid‐phase chemiluminescent immunoassays for diagnosis of endocrine diseases in animals. Comp Haematol Int. 1996;6(3):170–175.
  35. Singh AK, Jiang Y, White T, Spassova D. Validation of nonradioactive chemiluminescent immunoassay methods for the analysis of thyroxine and cortisol in blood samples obtained from dogs, cats, and horses. J Vet Diagn Invest. 1997;9(3):261–268.
    pubmed: 9249165
  36. Lewis JG, Bagley CJ, Elder PA, Bachmann AW, Torpy DJ. Plasma free cortisol fraction reflects levels of functioning corticosteroid‐binding globulin. Clin Chim Acta. 2005;359(1–2):189–194.
    pubmed: 15904907
  37. Hart KA, Kitchings KM, Kimura S, Norton NA, Myrna KE. Measurement of cortisol concentration in the tears of horses and ponies with pituitary pars intermedia dysfunction. Am J Vet Res. 2016;77(11):1236–1244.
    pubmed: 27805438
  38. Berghaus LJ, Cathcart J, Berghaus RD, Hart KA. Age‐related changes in vitamin D metabolism and vitamin D receptor expression in equine alveolar macrophages: a preliminary study. Vet Immunol Immunopathol. 2023;259:110593.
    pubmed: 37030152
  39. Helbig H, Berghaus LJ, Venner M, Berghaus R, Hart KA. Circulating concentrations of vitamins C, D and E vary with age but not with pneumonia status in foals during the first 5 months of life. Equine Vet J. 2025;57(6):1500–1510. 10.1111/evj.14480
    doi: 10.1111/evj.14480pubmed: 39888035google scholar: lookup
  40. nHooper‐McGrevy KE, Wilkie BN, Prescott JF. Immunoglobulin G subisotype responses of pneumonic and healthy, exposed foals and adult horses to virulence‐associated proteins. Clin Diagn Lab Immunol. 2003;10(3):345–351.n
    pmc: PMC154967pubmed: 12738629
  41. Ryan C, Giguère S. Equine neonates have attenuated humoral and cell‐mediated immune responses to a killed adjuvanted vaccine compared to adult horses. Clin Vaccine Immunol. 2010;17(12):1896–1902.
    pmc: PMC3008191pubmed: 20943883
  42. nKasuga‐Aoki H, Takai S, Sasaki Y, Tsubaki S, Madarame H, Nakane A. Tumour necrosis factor and interferon‐gamma are required in host resistance against virulent infection in mice: cytokine production depends on the virulence levels of n. Immunology. 1999;96(1):122–127.n
    pmc: PMC2326714pubmed: 10233686
  43. Mariella J, Castagnetti C, Prosperi A, Scagliarini A, Peli A. Cytokine levels in colostrum and in foals' serum pre‐ and post‐suckling. Vet Immunol Immunopathol. 2017;185:34–37.
    pubmed: 28242000
  44. nJacks S, Giguère S, Crawford PC, Castleman WL. Experimental infection of neonatal foals with triggers adult‐like gamma interferon induction. Clin Vaccine Immunol. 2007;14(6):669–677.n
    pmc: PMC1951072pubmed: 17409222
  45. Lopez BS, Hurley DJ, Giancola S, Giguère S, Hart KA. The effect of foal or adult horse plasma on equine monocyte‐derived dendritic cell phenotype and function. Vet Immunol Immunopathol. 2020;228:110099.
    pubmed: 32717449
  46. Flaminio MJ, Rush BR, Davis EG, Hennessy K, Shuman W, Wilkerson MJ. Characterization of peripheral blood and pulmonary leukocyte function in healthy foals. Vet Immunol Immunopathol. 2000;73(3–4):267–285.
    pubmed: 10713340
  47. Gern BH, Adams KN, Plumlee CR, Stoltzfus CR, Shehata L, Moguche AO, et al. TGFβ restricts expansion, survival, and function of T cells within the tuberculous granuloma. Cell Host Microbe. 2021;29(4):594–606.e6.
    pmc: PMC8624870pubmed: 33711270
  48. Wik JA, Skalhegg BS. T cell metabolism in infection. Front Immunol. 2022;13:840610.
    pmc: PMC8964062pubmed: 35359994
  49. Hart KA, Barton MH, Vandenplas ML, Hurley DJ. Effects of low‐dose hydrocortisone therapy on immune function in neonatal horses. Pediatr Res. 2011;70(1):72–77.
    pmc: PMC3111865pubmed: 21430601
  50. Lopez BS, Hurley DJ, Giancola S, Giguère S, Hart KA. The effect of cortisol on equine monocyte–derived dendritic cell phenotype and cytokine production. Vet Med Sci. 2024;10(2):e1333.
  51. Fratto MA, Hart KA, Norton NA, Barton MH, Giguère S, Hurley DJ. The effect of free and carrier‐bound cortisol on equine neutrophil function. Vet Immunol Immunopathol. 2017;183:16–21.
    pubmed: 28063472
  52. Murray MJ, Luba NK. Plasma gastrin and somatostatin, and serum thyroxine (T4), triiodothyronine (T3), reverse triiodothyronine (rT3) and cortisol concentrations in foals from birth to 28 days of age. Equine Vet J. 1993;25(3):237–239.
    pubmed: 8099543
  53. Hart KA, Dirikolu L, Ferguson DC, Norton NA, Barton MH. Daily endogenous cortisol production and hydrocortisone pharmacokinetics in adult horses and neonatal foals. Am J Vet Res. 2012;73(1):68–75.
    pubmed: 22204290
  54. Buonsenso D, Sali M, Pata D, Masiello E, Salerno G, Ceccarelli M, et al. Vitamin D levels in active TB, latent TB, non‐TB pneumonia and healthy children: a prospective observational study. Fetal Pediatr Pathol. 2018;37(5):337–347.
    pubmed: 30260729
  55. Gois PHF, Gois P, Ferreira D, Olenski S, Seguro A. Vitamin D and infectious diseases: simple bystander or contributing factor? Nutrients. 2017;9(7):651.
    pmc: PMC5537771pubmed: 28672783
  56. Holick MF. The vitamin D deficiency pandemic and consequences for nonskeletal health: mechanisms of action. Mol Aspects Med. 2008;29(6):361–368.
    pmc: PMC2629072pubmed: 18801384
  57. Dittmer KE, Thompson KG. Vitamin D metabolism and rickets in domestic animals: a review. Vet Pathol. 2011;48(2):389–407.
    pubmed: 20634407
  58. nLammer M. Detection of in feces and tracheobronchial secretions of foals on a farm with endemic Rhodococcosis: comparison of healthy foalos and foals with pulmonary abscesses. Veterinary School of Hanover. Hannover: University Of Veterinary Medicine Hanover; 2010. p. 116.
  59. Weimar B. Lung abscesses in Foals: Evaluation of Clinical, Ultrasonic, Endoscopial, Pathomorphological and Microbiological Findings. In Veterinary School of Hanover. Hanover University. p. 157. 2006.
  60. Goebel B, Freise F, Venner M. Microbiological findings in tracheobronchial mucus samples and in the feces of foals with pneumonia at Pferdeheilkunde. 2023;39(1):37–42.
  61. Thakur A, Mikkelsen H, Jungersen G. Intracellular pathogens: host immunity and microbial persistence strategies. J Immunol Res. 2019;2019:1356540.
    pmc: PMC6487120pubmed: 31111075

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