Cytokine profiles of peripheral blood mononuclear cells isolated from septic and healthy neonatal foals

Abstract

Background: Septicemia initiates the production of pro-inflammatory (interleukin [IL] 1-beta [IL-1β], interferon-gamma [IFN-γ], IL-6), and anti-inflammatory (IL-4) cytokines. The transcription of some of these proteins (IL-8, IL-6) is linked to endotoxin-induced activation of the toll-like receptor 4 (TLR4) on peripheral blood mononuclear cells (PBMC). Hypotheses: Septic foals fail to increase gene expression of IFN-y. Nonsurviving septic foals exhibit distinctive cytokine profiles. Animals: Twenty-one septic and 20 healthy neonatal foals. Methods: Using real-time polymerase chain reaction, gene expression of IFN-γ, IL-1β, IL-6, IL-4, IL-8, TLR4, and β-actin in PBMC were measured in samples obtained from septic foals at 0, 24, and 72 hours (T = 0, 24, and 72 hours) after admission to the Cornell University Hospital for Animals. Control foals were sampled at comparable times. Results: At T = 0 hours, septic foals exhibited a 6-fold decrease in gene expression of IL-4 and a 5-fold increase in gene expression of TLR4. Gene expression of IFN-γ, IL-6, IL-8, or of IL-1β did not differ between the 2 groups of foals at T = 0 hours. In septic foals that died (n = 3), there was a 15-fold increase in IL-6 at T = 0 hours compared to survivors. Conclusions and Clinical Importance: Septic foals, unlike septic human infants, up-regulate TLR4 gene expression, which may enhance pro-inflammatory cytokine production. Despite the presence of sepsis, IFN-γ was not up-regulated. Additional studies are needed to verify that increased IL-6 expression is associated with a poor prognosis in septic foals. Copyright © 2007 by the American College of Veterinary Internal Medicine.