N‐Terminal Pro‐C‐Natriuretic Peptide and Cytokine Kinetics in Dogs with Endotoxemia

Abstract

BackgroundSerum N‐terminal pro‐C‐natriuretic peptide (NT‐proCNP) concentration at hospital admission has sufficient sensitivity and specificity to differentiate naturally occurring sepsis from nonseptic systemic inflammatory response syndrome (SIRS). However, little is known about serum NT‐proCNP concentrations in dogs during the course of sepsis.ObjectiveTo determine serum NT‐proCNP and cytokine kinetics in dogs with endotoxemia, a model of canine sepsis.SamplesEighty canine serum samples.MethodsEight healthy adult Beagles were randomized to receive Escherichia coli lipopolysaccharide (LPS, 5 μg/kg) or placebo (0.9% NaCl) as a single IV dose in a randomized crossover study. Serum collected at 0, 1, 2, 4, and 24 hours was stored at −80°C for batch analysis. Serum NT‐proCNP was measured by ELISA and 13 cytokines and chemokines by multiplex magnetic bead‐based assay.ResultsSerum NT‐proCNP concentrations did not differ significantly between LPS‐ and placebo‐treated dogs at any time. When comparing serum cytokine concentrations, LPS‐treated dogs had higher interleukin‐6 (IL‐6), IL‐10, TNF‐α and KC‐like at 1, 2, and 4 hours; higher CCL2 at 1, 2, 4, and 24 hours; and higher IL‐8 and CXCL10 at 4 hours compared to placebo‐treated dogs. There were no differences in serum GM‐CSF, IFN‐γ, IL‐2, IL‐7, IL‐15 or IL‐18 between LPS‐ and placebo‐treated dogs.Conclusions and Clinical ImportanceSerum NT‐proCNP concentration does not change significantly in response to LPS administration in healthy dogs. Certain serum cytokine and chemokine concentrations are significantly increased within 1–4 hours after LPS administration and warrant further investigation as tools for the detection and management of sepsis in dogs.

Serum alpha1‐proteinase inhibitor concentrations in dogs with systemic inflammatory response syndrome or sepsis

“…Proinflammatory cytokines IL‐6 and TNF‐α were also evaluated in this study. The increase in plasma IL‐6 concentration in dogs with SIRS/sepsis but its inability to differentiate septic dogs from those with noninfectious SIRS is consistent with previous studies in dogs but contrasts the results of other studies showing IL‐6 to have prognostic potential in dogs with SIRS/sepsis . Also, a cause‐and‐effect relationship between IL‐6 and cα 1 ‐PI cannot be confirmed based on the results of this study, as cytokines and APP can influence the expression and release of one another, and the signaling pathways involved in systemic inflammation and infection are complex and characterized by a moderate degree of redundancy …”

“…Proinflammatory cytokines such as interleukin‐6 (IL‐6), which induces mainly type II APPs, and tumor necrosis factor‐alpha (TNF‐α), which induces type I APPs, have been demonstrated to be upregulated in dogs with sepsis or noninfectious systemic inflammatory response syndrome (SIRS) but not to distinguish between them . C‐reactive protein (CRP), a type I APP of the pentraxin family, has been shown to have prognostic utility in dogs with sepsis or SIRS but also lacks the ability to discriminate sepsis from noninfectious SIRS …”

Serial Evaluation of Abdominal Fluid and Serum Amino‐terminal pro‐C‐type Natriuretic Peptide in Dogs with Septic Peritonitis

“…In this study, the reported interassay CV (14.4–15.1%) was similar to a previously reported interassay CV for use of this ELISA on canine serum,16 when higher CVs were obtained with the lowest NT‐proCNP concentrations.…”

Neutrophil gelatinase‐associated lipocalin in dogs with chronic kidney disease, carcinoma, lymphoma and endotoxaemia

“…All 15 dogs that were administered LPS were hypothermic, lethargic, and had gastrointestinal signs of hypersalivation and diarrhoea within 2 hours of administration. Clinical parameters and cytokine concentrations in LPS‐treated dogs were consistent with systemic inflammation (Floras et al , Gauthier et al , ).…”

“…Serum was also collected from the dogs at 4 and 24 hours post‐LPS administration. Parameters that were serially monitored after administration of LPS for the purposes of the other studies included cytokine concentrations, packed cell volume, total plasma protein, lactate and colloid osmotic pressure as well as rectal temperature, heart rate, respiratory rate and blood pressure (Floras et al , Gauthier et al , ).…”