Cytokine dysregulation in aged horses and horses with pituitary pars intermedia dysfunction.
Abstract: Equine pituitary pars intermedia dysfunction (PPID) is the result of a loss of dopaminergic inhibition of the pars intermedia secondary to neurodegeneration of periventricular hypothalamic neurons. The pathologic events contributing to development of neurodegeneration or clinical signs in equids with PPID are unknown. Chronic inflammation may contribute to initiation or progression of PPID. Objective: Horses with PPID have a distinct systemic cytokine profile compared with that of normal adult or aged horses. The cytokine profile of healthy aged horses differs from that of adult horses. Methods: Aged horses with PPID, healthy aged-matched controls, and adult controls (n = 14 per group). Methods: Total leukocyte cytokine expression was determined by quantitative polymerase chain reaction (PCR), and tumor necrosis factor (TNF)-alpha plasma concentration was determined by enzyme-linked immunosorbent assay (ELISA). Peripheral blood mononuclear cell (PBMC) TNF-alpha response after endotoxin (lipopolysaccharide [LPS]) treatment was assessed by ELISA. Results: Aged healthy horses had increased expression of interleukin (IL)-6, IL-8, and interferon-gamma as well as PBMC TNF-alpha release after LPS stimulation compared with healthy adult horses. In contrast, aged horses with PPID had increased IL-8 expression, but expression of other cytokines was similar to that of healthy adult horses, not age-matched controls. Conclusions: Aged horses show evidence of a proinflammatory state that may contribute to development of age-associated diseases. Horses with PPID have increased expression of IL-8, which may influence the ability of horses with PPID to respond to bacterial pathogens. The general decrease in proinflammatory cytokine expression observed in horses with PPID may be the outcome of high plasma concentrations of anti-inflammatory hormones.
Publication Date: 2008-03-29 PubMed ID: 18371032DOI: 10.1111/j.1939-1676.2008.0076.xGoogle Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
- Age Factors
- Clinical Study
- Cytokines
- Diagnostic Technique
- Disease Etiology
- Equine Diseases
- Equine Health
- Geriatric Horses
- Horses
- Immune Response
- Immune System
- In Vivo
- Inflammation
- Inflammatory Response
- Interleukins
- Pathophysiology
- Pituitary Pars Intermedia Dysfunction
- Tumor Necrosis Factor
- Veterinary Medicine
- Veterinary Research
Summary
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The research article explores how aging and a condition known as Equine Pituitary Pars Intermedia Dysfunction (PPID) influence the regulation of cytokines (small proteins involved in cell signaling) in horses. The study also assesses the difference in cytokine profiles among PPID affected horses, healthy aged horses, and adult horses.
Objective of the Research
- The scientists conducted this study with the primary intent of establishing if horses suffering from PPID exhibit a unique systemic cytokine profile compared to normal adult or aged equines.
- The research also aimed to find out if the cytokine profile of a healthy ageing horse significantly differs from that of an adult horse.
Methodological Approach
- The researchers chose three separate groups of horses for the study: aged horses afflicted with PPID, healthy aged-matched controls, and adult controls. Each group had 14 members.
- The total leukocyte (white blood cells) cytokine expression was determined through a process known as quantitative polymerase chain reaction (PCR), which measures the amount of a specific type of DNA.
- The concentration of tumor necrosis factor (TNF)-alpha, a cell signaling protein (cytokine) involved in systemic inflammation, in the plasma of the horses was determined using the enzyme-linked immunosorbent assay (ELISA), a test that measures immune responses in the body.
- Peripheral blood mononuclear cells (PBMC) from the subject horses were also assessed for their TNF-alpha response after endotoxin (lipopolysaccharide [LPS]) treatment using ELISA.
Findings of the Study
- The findings showed that healthy aged horses had an increased expression of interleukin (IL)-6, IL-8, and interferon-gamma, as well as PBMC TNF-alpha release after LPS stimulation compared with healthy adult horses.
- However, aged horses with PPID displayed increased IL-8 expression, but the expression of other cytokines was similar to that of healthy adult horses, not aged-matched controls.
Conclusions Drawn from the Study
- The research concludes that aged horses show signs of being in a pro-inflammatory state, which might contribute to the development of age-associated ailments.
- PPID-affected horses show increased expression of IL-8, suggesting this might influence these equines’ ability to counter bacterial pathogens.
- A general decrease in the expression of pro-inflammatory cytokines was noticed in horses suffering from PPID, which could potentially be the result of high plasma concentrations of anti-inflammatory hormones.
Cite This Article
APA
McFarlane D, Holbrook TC.
(2008).
Cytokine dysregulation in aged horses and horses with pituitary pars intermedia dysfunction.
J Vet Intern Med, 22(2), 436-442.
https://doi.org/10.1111/j.1939-1676.2008.0076.x Publication
Researcher Affiliations
- Department of Physiological Sciences, Oklahoma State University, Stillwater, OK 74078, USA. diannem@okstate.edu
MeSH Terms
- Aging / physiology
- Animals
- Cytokines / genetics
- Cytokines / metabolism
- Gene Expression Regulation
- Horse Diseases / metabolism
- Horses
- Pituitary Diseases / metabolism
- Pituitary Diseases / physiopathology
- Pituitary Diseases / veterinary
- Pituitary Gland / physiopathology
- Pituitary Gland, Intermediate / metabolism
- Pituitary Gland, Intermediate / physiopathology
- RNA, Messenger / metabolism
- Tumor Necrosis Factor-alpha / blood
- Tumor Necrosis Factor-alpha / metabolism
Citations
This article has been cited 13 times.- DeNotta S, McFarlane D. Immunosenescence and inflammaging in the aged horse. Immun Ageing 2023 Jan 6;20(1):2.
- Kirkwood NC, Hughes KJ, Stewart AJ. Pituitary Pars Intermedia Dysfunction (PPID) in Horses. Vet Sci 2022 Oct 10;9(10).
- Latham CM, Owen RN, Dickson EC, Guy CP, White-Springer SH. Skeletal Muscle Adaptations to Exercise Training in Young and Aged Horses. Front Aging 2021;2:708918.
- Simões J, Batista M, Tilley P. The Immune Mechanisms of Severe Equine Asthma-Current Understanding and What Is Missing. Animals (Basel) 2022 Mar 16;12(6).
- 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.
- Edler MK, Mhatre-Winters I, Richardson JR. Microglia in Aging and Alzheimer's Disease: A Comparative Species Review. Cells 2021 May 8;10(5).
- Bond SL, Hundt J, Léguillette R. Effect of injected dexamethasone on relative cytokine mRNA expression in bronchoalveolar lavage fluid in horses with mild asthma. BMC Vet Res 2019 Nov 6;15(1):397.
- Bond S, Léguillette R, Richard EA, Couetil L, Lavoie JP, Martin JG, Pirie RS. Equine asthma: Integrative biologic relevance of a recently proposed nomenclature. J Vet Intern Med 2018 Nov;32(6):2088-2098.
- Rütten S, Schusser GF, Abraham G, Schrödl W. Release kinetics of tumor necrosis factor-α and interleukin-1 receptor antagonist in the equine whole blood. BMC Vet Res 2016 Jun 17;12(1):117.
- Clark KC, Kol A, Shahbenderian S, Granick JL, Walker NJ, Borjesson DL. Canine and Equine Mesenchymal Stem Cells Grown in Serum Free Media Have Altered Immunophenotype. Stem Cell Rev Rep 2016 Apr;12(2):245-56.
- Carrade DD, Lame MW, Kent MS, Clark KC, Walker NJ, Borjesson DL. Comparative Analysis of the Immunomodulatory Properties of Equine Adult-Derived Mesenchymal Stem Cells(). Cell Med 2012;4(1):1-11.
- Vaughn SA, Lemons MB, Hart KA. The Effect of Season and Breed on Hypothalamic-Pituitary-Adrenal Axis Hormones, Metabolic Hormones, and Oxidative Markers in Ponies and Horses. J Vet Intern Med 2025 Mar-Apr;39(2):e70047.
- Hobbs KJ, Le Sueur ANV, Burke MJ, Cooper BL, Sheats MK, Ueda Y. Feasibility of hemoperfusion using extracorporeal therapy in the horse. Front Vet Sci 2024;11:1414426.
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