Domestic animal endocrinology2020; 74; 106531; doi: 10.1016/j.domaniend.2020.106531

Effects of pituitary pars intermedia dysfunction and Prascend (pergolide tablets) treatment on endocrine and immune function in horses.

Abstract: It remains unclear how pituitary pars intermedia dysfunction (PPID) and pergolide treatment (Prascend [pergolide tablets]) affect endocrine and immune function in horses. To evaluate these effects, blood was collected regularly from 28 university-owned horses (10 Non-PPID, 9 PPID control [PC], and 9 PPID treatment [PT]) over approximately 15 mo. Pergolide treatment was initiated after Day 0 collections. Analyses included ACTH, insulin, total cortisol, free cortisol, complete blood counts, plasma myeloperoxidase, and cytokine/receptor gene expression in basal whole blood and in vitro stimulations (PMA/ionomycin, heat-inactivated Rhodococcus equi, and heat-inactivated Escherichia coli) of whole blood and peripheral blood mononuclear cells (PBMCs). The results were analyzed using a linear mixed model (SAS 9.4) with significance set at P < 0.05. Significant group (P = 0.0014) and group-by-time (P = 0.0004) effects were observed in resting ACTH such that PT horses differed from Non-PPID horses only at Day 0. PT horses had significantly lower changes in ACTH responses to thyrotropin-releasing hormone stimulation tests than PC horses at non-fall time points only, mid-late February 2018 (P = 0.016) and early April 2018 (P = 0.0172). When PT and PC horses did not differ, they were combined before comparison to Non-PPID horses. No significant group or group-by-time effects were seen in resting insulin, total cortisol, or free cortisol; however, significant time effects were observed in these measures. PPID horses had lower absolute lymphocyte (P = 0.028) and red blood cell (P = 0.0203) counts than Non-PPID horses. In unstimulated whole blood, PPID horses had increased IL-8 expression compared with Non-PPID horses (P = 0.0102). In addition, PPID horses had decreased interferon γ production from PBMCs after stimulation with R. equi (P = 0.0063) and E. coli (P = 0.0057) and showed increased transforming growth factor β expression after E. coli stimulation (P = 0.0399). The main limitations of this study were a limited sample size and an inability to truly randomize the PPID horses into treatment groups. Resting ACTH is likely the best choice for determining successful responses to pergolide. Neither PPID nor pergolide appears to influence insulin, total cortisol, and free cortisol. As measured, systemic immune function was altered in PPID horses, and it is likely that these horses are indeed at increased risk of opportunistic infection. Despite reducing ACTH, pergolide treatment did not appear to influence immune function.
Publication Date: 2020-07-29 PubMed ID: 32942194DOI: 10.1016/j.domaniend.2020.106531Google Scholar: Lookup
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  • Clinical Trial
  • Veterinary
  • Journal Article
  • Research Support
  • Non-U.S. Gov't

Summary

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The research study investigates the effects of Pituitary Pars Intermedia Dysfunction (PPID) and pergolide treatment on the endocrine and immune systems of horses. The outcomes reveal the PPID horses tend to have altered systemic immune function, while neither PPID nor the pergolide treatments influence insulin, total cortisol, and free cortisol.

Study Participants and Methods

  • Blood samples were collected from 28 university-owned horses divided into three groups: Non-PPID horses, PPID control horses (PC), and PPID treatment horses (PT). The study spanned over approximately 15 months.
  • The PT group began pergolide treatment after day zero collections.
  • Various analyses were carried out on these blood samples, including ACTH, insulin, total cortisol, free cortisol, complete blood counts, plasma myeloperoxidase, and cytokine/receptor gene expression in basal whole blood and in in-vitro stimulations using PMA/ionomycin, heat-inactivated Rhodococcus equi, and heat-inactivated Escherichia coli of whole blood and peripheral blood mononuclear cells (PBMCs).

Results and Findings

  • The results were significant for ACTH where the PT group differed from the Non-PPID group only on the first day of treatment. At non-fall time points only, PT horses showed substantially lower changes in ACTH responses to thyrotropin-releasing hormone stimulation tests than PC horses.
  • No significant group or group-by-time effects were observed in resting insulin, total cortisol, or free cortisol. Nonetheless, time effects were noticeable in these measures.
  • PPID horses had lower absolute lymphocyte and red blood cell counts than Non-PPID horses. They also exhibited increased IL-8 expression in unstimulated whole blood.
  • When stimulated with R. equi and E. coli, PPID horses showed decreased interferon γ production from PBMCs and increased transforming β expression after E. coli stimulation.
  • The best choice for determining successful responses to pergolide appears to be resting ACTH.

Ideal Areas for Future Research

  • This study’s limitations include a small sample size and the inability to truly randomize the PPID horses into treatment groups.
  • The PPID horses appear to be at a greater risk of opportunistic infection. The pergolide treatment, despite reducing ACTH, did not seem to affect immune function.

Cite This Article

APA
Miller AB, Loynachan AT, Bush HM, Hart KA, Barker VD, Campana-Emard AG, Grubbs ST, Adams AA. (2020). Effects of pituitary pars intermedia dysfunction and Prascend (pergolide tablets) treatment on endocrine and immune function in horses. Domest Anim Endocrinol, 74, 106531. https://doi.org/10.1016/j.domaniend.2020.106531

Publication

ISSN: 1879-0054
NlmUniqueID: 8505191
Country: United States
Language: English
Volume: 74
Pages: 106531
PII: S0739-7240(20)30098-9

Researcher Affiliations

Miller, A B
  • M.H. Gluck Equine Research Center, Department of Veterinary Science, University of Kentucky, Lexington, KY, USA. Electronic address: ashton.miller@uky.edu.
Loynachan, A T
  • Veterinary Diagnostic Laboratory, Department of Veterinary Science, University of Kentucky, Lexington, KY, USA.
Bush, H M
  • Department of Biostatistics, University of Kentucky, Lexington, KY, USA.
Hart, K A
  • Department of Large Animal Medicine, College of Veterinary Medicine, University of Georgia, Athens, GA, USA.
Barker, V D
  • M.H. Gluck Equine Research Center, Department of Veterinary Science, University of Kentucky, Lexington, KY, USA.
Campana-Emard, A G
  • M.H. Gluck Equine Research Center, Department of Veterinary Science, University of Kentucky, Lexington, KY, USA.
Grubbs, S T
  • Boehringer Ingelheim Animal Health USA, Inc, Duluth, GA, USA.
Adams, A A
  • M.H. Gluck Equine Research Center, Department of Veterinary Science, University of Kentucky, Lexington, KY, USA.

MeSH Terms

  • Adrenocorticotropic Hormone / blood
  • Adrenocorticotropic Hormone / metabolism
  • Animals
  • Dose-Response Relationship, Drug
  • Female
  • Horse Diseases / blood
  • Horse Diseases / drug therapy
  • Horses
  • Hypertrichosis / drug therapy
  • Hypertrichosis / etiology
  • Hypertrichosis / veterinary
  • Male
  • Pergolide / administration & dosage
  • Pergolide / therapeutic use
  • Pituitary Diseases / complications
  • Pituitary Diseases / drug therapy
  • Pituitary Diseases / veterinary
  • Pituitary Gland, Intermediate / metabolism

Citations

This article has been cited 7 times.
  1. Zapf AM, Fey K, Bu00fcttner K, Gru00f6f M, Staszyk C. Periodontal structures in horses with pituitary pars intermedia dysfunction: A histological evaluation.. Front Vet Sci 2023;10:1114445.
    doi: 10.3389/fvets.2023.1114445pubmed: 36733635google scholar: lookup
  2. Kirkwood NC, Hughes KJ, Stewart AJ. Prospective Case Series of Clinical Signs and Adrenocorticotrophin (ACTH) Concentrations in Seven Horses Transitioning to Pituitary Pars Intermedia Dysfunction (PPID).. Vet Sci 2022 Oct 17;9(10).
    doi: 10.3390/vetsci9100572pubmed: 36288186google scholar: lookup
  3. Kirkwood NC, Hughes KJ, Stewart AJ. Pituitary Pars Intermedia Dysfunction (PPID) in Horses.. Vet Sci 2022 Oct 10;9(10).
    doi: 10.3390/vetsci9100556pubmed: 36288169google scholar: lookup
  4. Zhang T, Xi Y, Wu T, Liu J. Nuclear Transporting Factor 2 as a Novel Biomarker of Head and Neck Squamous Cell Carcinoma and Associated with T/B Cell Receptor Signaling Pathway.. Biomed Res Int 2022;2022:2885323.
    doi: 10.1155/2022/2885323pubmed: 35155672google scholar: lookup
  5. Kam YN, McKenzie K, Coyle M, Bertin FR. Repeatability of a thyrotropin-releasing hormone stimulation test for diagnosis of pituitary pars intermedia dysfunction in mature horses.. J Vet Intern Med 2021 Nov;35(6):2885-2890.
    doi: 10.1111/jvim.16281pubmed: 34642962google scholar: lookup
  6. Guarino C, Pinn-Woodcock T, Levine DG, Miller J, Johnson AL. Case Report: Nuchal Bursitis Associated With Borrelia burgdorferi Infection in a Horse.. Front Vet Sci 2021;8:743067.
    doi: 10.3389/fvets.2021.743067pubmed: 34631864google scholar: lookup
  7. Miller AB, Harris PA, Barker VD, Adams AA. Short-term transport stress and supplementation alter immune function in aged horses.. PLoS One 2021;16(8):e0254139.
    doi: 10.1371/journal.pone.0254139pubmed: 34411137google scholar: lookup