Portions of this work were presented at the 25th American College of Veterinary Internal Medicine Forum, June 2007, Seattle, WA.
Cytokine Dysregulation in Aged Horses and Horses with Pituitary Pars Intermedia Dysfunction
Article first published online: 27 MAR 2008
Copyright © 2008 by the American College of Veterinary Internal Medicine
Journal of Veterinary Internal Medicine
Volume 22, Issue 2, pages 436–442, March–April 2008
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How to Cite
McFarlane, D. and Holbrook, T.C. (2008), Cytokine Dysregulation in Aged Horses and Horses with Pituitary Pars Intermedia Dysfunction. Journal of Veterinary Internal Medicine, 22: 436–442. doi: 10.1111/j.1939-1676.2008.0076.x
- Issue published online: 27 MAR 2008
- Article first published online: 27 MAR 2008
- Submitted June 27, 2007; Revised October 5, 2007; Accepted November 19, 2007.
- Equine Cushing's disease;
Background: 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.
Hypothesis: 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.
Animals: 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)-α plasma concentration was determined by enzyme-linked immunosorbent assay (ELISA). Peripheral blood mononuclear cell (PBMC) TNF-α 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-γ as well as PBMC TNF-α 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 and Clinical Importance: 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.