Cytokine profiles of peripheral blood mononuclear cells isolated from septic and healthy neonatal foals.
BACKGROUND
Septicemia initiates the production of pro-inflammatory (interleukin [IL] 1-beta [IL-1beta], interferon-gamma [IFN-gamma], 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).


OBJECTIVE
Septic foals fail to increase gene expression of IFN-gamma. Nonsurviving septic foals exhibit distinctive cytokine profiles.


METHODS
Twenty-one septic and 20 healthy neonatal foals.


METHODS
Using real-time polymerase chain reaction, gene expression of IFN-gamma, IL-1beta, IL-6, IL-4, IL-8, TLR4, and beta-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-gamma, IL-6, IL-8, or of IL-1beta 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
Septic foals, unlike septic human infants, up-regulate TLR4 gene expression, which may enhance pro-inflammatory cytokine production. Despite the presence of sepsis, IFN-gamma was not up-regulated. Additional studies are needed to verify that increased IL-6 expression is associated with a poor prognosis in septic foals.
Gold
Jenifer R
JR
Bend Equine Medical Clinic, Bend, OR, USA.
Perkins
Gillian A
GA
Erb
Hollis N
HN
Ainsworth
Dorothy M
DM
D000818:Animals; D000831:Animals, Newborn; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D016207:Cytokines / Q000378:metabolism*; D005260:Female; D015870:Gene Expression; D006734:Horse Diseases / Q000097:blood / Q000276:immunology*; D006736:Horses / Q000097:blood / Q000276:immunology*; D015847:Interleukin-4 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D008297:Male; D016133:Polymerase Chain Reaction / Q000379:methods / Q000662:veterinary; D018805:Sepsis / Q000097:blood / Q000276:immunology / Q000662:veterinary*; D012720:Severity of Illness Index; D013997:Time Factors; D051197:Toll-Like Receptor 4 / Q000378:metabolism*; D015854:Up-Regulation
D015415:Biomarkers; D016207:Cytokines; D015850:Interleukin-6; D051197:Toll-Like Receptor 4; D015847:Interleukin-4