Association of Adrenocorticotrophin and Cortisol Concentrations with Peripheral Blood Leukocyte Cytokine Gene Expression in Septic and Nonseptic Neonatal Foals

Abstract

Background: The hypothalamic-pituitary-adrenal (HPA) is influenced by the proinflammatory cytokines IL-6, IL-1b, and TNF-a in critically ill humans. Information about the association of cytokines with the HPA axis in neonatal foals is lacking.Hypothesis/Objectives: The objectives were to describe for hospitalized septic and nonseptic foals (1) temporal changes in blood concentrations of ACTH, and cortisol, and leukocyte cytokine gene expression, and (2) coassociation of these HPA axis hormones with blood leukocyte cytokine gene expression.Animals: Hospitalized septic foals (N = 15) and hospitalized nonseptic foals (N = 11).Methods: Blood samples, obtained from study foals at admission (T = 0), and 24 (T = 1), 48 (T = 2), 72 (T = 3), and 96 (T = 4) hours after admission, were processed to isolate RNA from leukocytes and to harvest plasma and serum for hormone assays. Plasma ACTH and serum cortisol concentrations were determined by radioimmunoassay. Leukocyte mRNA expression of IL-1b IL-6, IL-8, IL-10, and TNF-a was determined using RT-PCR.Results: Cortisol concentrations were greater (P < .05) in foals at admission than at other time points. The expressions of IL-8 and IL-10 mRNA were lower (P < .05) at each time point in septic than in nonseptic foals. Among septic foals, ACTH was positively associated (P = .0026) with IL-6 mRNA expression.Conclusions: Sepsis influences secretion of the HPA axis hormones and expression of cytokines in foals. A positive association with the HPA axis and IL-6 expression was detected. The clinical importance of these findings requires additional study.

Renin‐Angiotensin‐Aldosterone System and Hypothalamic‐Pituitary‐Adrenal Axis in Hospitalized Newborn Foals

“…RAI is likely to enhance ACTH release because of a lack of cortisol‐mediated suppression of the HPAA. In a recent study, ACTH concentrations were positively correlated with IL‐6 mRNA expression in septic foals …”

“…The negative correlation between aldosterone concentration and clinical evidence of hypoperfusion supports relative hypoaldosteronism as a part of RAI, because increased aldosterone concentrations would have been expected. High variability in ACTH, cortisol, and aldosterone concentrations associated with an early or late stage of sepsis exists in neonatal foals . Therefore, our definition of relative hypoaldosteronism based solely on high ACTH/aldosterone should be interpreted with caution.…”

Detection of bacteraemia and host response in healthy neonatal foals

“…In a separate report, IL‐8 expression was lower in septic vs. nonseptic foals, though not associated with survival . Increased IL‐10 gene expression has been associated with death or euthanasia of foals with neonatal disease in one report , although others have had conflicting results . Interleukin 8 gene expression was greater in diseased foals <5 days old, although sampling times of controls were not reported .…”

“…In disease, IL‐1 and IL‐8 expression was correlated to clinicopathological variables in septic foals . In a separate report, IL‐8 expression was lower in septic vs. nonseptic foals, though not associated with survival . Increased IL‐10 gene expression has been associated with death or euthanasia of foals with neonatal disease in one report , although others have had conflicting results .…”

Dynamic expression of leukocyte innate immune genes in whole blood from horses with lipopolysaccharide-induced acute systemic inflammation

“…In foals, several studies have been conducted comparing innate gene expressions in blood leukocytes in septic patients versus non-septic [7–9] and healthy foals [10, 11]. In adult horses leukocyte immune genes have been correlated to type of disease and outcome in patients with gastrointestinal inflammation and strangulation [12] while a small number of studies have had a primary aim of investigating leukocyte innate immune gene expressions in experimental lipopolysaccharide- (LPS-) induced systemic inflammation [13–15].…”