Plasma Inflammatory Mediator Concentrations at ICU Admission in Dogs with Naturally Developing Sepsis

Abstract

Background: Identifying biomarkers to aide in the diagnosis and prognostication of sepsis in dogs would be valuable to veterinarians.Objective: To compare plasma inflammatory mediator concentrations among dogs with sepsis, noninfectious systemic inflammatory response syndrome (NSIRS), and healthy dogs.Animals: Dogs with sepsis (n = 22), NSIRS (n = 23), and healthy dogs (n = 13) presenting to the intensive care unit (ICU) at a veterinary teaching hospital.Methods: Prospective observational study. Clinical parameters were recorded for each dog and plasma tumor necrosis factor (TNF) bioactivity and concentrations of interleukin (IL)-6, CXC chemokine ligand (CXCL)-8 and IL-10 were determined at ICU presentation.Results: Dogs with sepsis and NSIRS were significantly more likely to have measurable TNF activity (sepsis 20/22; NSIRS 19/20; healthy 0/13) and IL-6 concentration (sepsis 12/22; NSIRS 15/23; healthy 2/13), than healthy dogs. Healthy dogs (9/13) were significantly more likely to have measurable plasma IL-10 concentrations than dogs with sepsis (4/19), but not NSIRS (7/20). None of the inflammatory mediators evaluated had optimal sensitivity or specificity for the diagnosis of sepsis. Twelve of 22 dogs with sepsis and 15/23 dogs with NSIRS survived to discharge; none of the measured biomarkers correlated with survival to discharge.Conclusions and Clinical Importance: Sepsis and NSIRS are associated with increased production of the proinflammatory cytokines TNF and IL-6. In addition, sepsis is associated with decreased production of the anti-inflammatory cytokine IL-10. Despite this, plasma TNF, IL-6, CXCL-8, and IL-10 measured at ICU presentation do not appear to be valuable biomarkers to differentiate sepsis from NSIRS, or predict hospital outcome.

Assessment of Serum Myokines and Markers of Inflammation Associated with Exercise in Endurance Racing Sled Dogs

“…Similar increases into the 10–25 μg/mL range have been observed in sprint sled dogs 24 hours after participating in a 16‐mile sprint race . One would also expect that other inciting causes, such as infection and inflammation related changes in IL‐6 or TNF‐α, might induce this CRP response; however, the lack of a detectable response of TNF‐α and lack of detectable changes in IL‐6 indicates that infectious or serious exercise‐induced inflammation is not the source of elevated CRP . Additional investigation is needed to determine the mechanisms of induction of the APR, which do not appear to be related to IL‐6, as has been suggested in human endurance athletes …”

Prospective evaluation of the acute patient physiologic and laboratory evaluation score and an extended clinicopathological profile in dogs with systemic inflammatory response syndrome

“…Systemic inflammatory response syndrome (SIRS) and sepsis are frequently observed conditions in critically ill human patients . Despite the lack of data on the prevalence of SIRS in veterinary patients, this syndrome has gained increasing attention and interest in recent years . SIRS is characterized by activation of the acute phase response, hemostatic derangements, impaired tissue perfusion and oxygenation, and can ultimately progress to multiple organ dysfunction syndrome and death .…”

“…Despite the lack of data on the prevalence of SIRS in veterinary patients, this syndrome has gained increasing attention and interest in recent years . SIRS is characterized by activation of the acute phase response, hemostatic derangements, impaired tissue perfusion and oxygenation, and can ultimately progress to multiple organ dysfunction syndrome and death . Despite advances in supportive care, SIRS and sepsis remain leading causes of mortality in the ICU setting, with overall mortality rates ranging from 27% to 64% in dogs .…”

Increased concentrations of C-reactive protein but not high-mobility group box 1 in dogs with naturally occurring sepsis

“…Several biomarkers have previously been evaluated in canine SIRS or sepsis including procalcitonin, tumor necrosis factor α (TNF-α), interleukin 6 (IL-6), 4 interleukin 10 (IL-10), interleukin 8 (IL-8), endotoxin indicator prostaglandin F 2α metabolite (PGM) and a well-known inflammatory marker C-reactive protein (CRP) (Hagman et al, 2006a, Fransson et al, 2007, Nakamura et al, 2008, Yilmaz et al, 2008, DeClue et al, 2012and Karlsson et al, 2012. However, none of the biomarkers studied in humans has yet been shown to differentiate non-infectious SIRS from sepsis in a clinical setting (Pierrakos andVincent, 2010 andHall et al, 2011).…”