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‐β], 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‐γ. 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.