Cytokine and Chemokine Profiling in Cats With Sepsis and Septic Shock

Abstract

Background: Sepsis is a life-threatening condition associated with an exacerbated production of both pro-and anti-inflammatory cytokines that can promote a hyperactive response to infection or induce immunoparalysis. Data regarding the immune response to sepsis in cats are scarce. Establishing the profiles of cytokines and chemokines in feline sepsis to characterize the nature of the immune responses to sepsis might enable individualized treatments to be developed and targeted. Objective: To evaluate the cytokine and chemokine network in cats with sepsis and septic shock, and to investigate the associations of these analytes with disease severity and outcome. Methods: Blood samples prospectively collected at presentation of cats with sepsis and septic shock to two veterinary teaching hospitals were analyzed. Forty healthy cats were included as controls. A 19-plex feline cytokine/chemokine magnetic bead assay system was used to measure analytes in citrated plasma samples. Cytokine concentrations were compared between groups using the Kruskal-Wallis test with Dunn's post-hoc correction for multiple comparisons. Cytokine concentrations were compared between survivors and non-survivors with the Mann-Whitney U test. Odds ratios were calculated using logistic regression. A multivariable logistic regression model for prediction of septic shock was constructed. Results: The study enrolled 35 septic cats. Many cytokines were undetectable in both sick and healthy control cats and were excluded from subsequent analyses. Comparisons of cytokine concentrations among healthy controls, cats with sepsis (n = 12) and cats with septic shock (n = 23) revealed that sick cats (sepsis or septic shock) had significantly higher plasma concentrations of IL-6, IL-8, KC-like, and RANTES compared to healthy controls. The combination of MCP-1, Flt-3L, and IL-12 was predictive of septic shock. None of the cytokines analyzed was predictive of outcome in this study population. Conclusion: Plasma concentrations of IL-6, IL-8, KC-like, and RANTES are increased in cats with sepsis and may play important roles in pathogenesis. Multivariable modeling suggested that analysis of cytokines might aid differentiation of septic shock from sepsis. None of the cytokines analyzed was predictive of outcome. Measurement of these cytokines might enable future studies to better diagnose and characterize feline sepsis and septic shock.

Classification of Septic Shock Phenotypes Based on the Presence of Hypotension and Hyperlactatemia in Cats

“…On the contrary, SAA concentration was comparable between cats with uncomplicated sepsis and septic shock, as well as between survivors and non-survivors. Similar results had been previously reported, and indicate that despite SAA having a great value to recognize systemic inflammation in cats, its prognostic utility seems poor (15,17).…”

“…Demographic data, sepsis etiologies and mortality rates in our study population were comparable with the results of previous studies in septic cats ( 2 , 3 , 15 , 17 , 19 , 20 ). Moreover, we were able to identify all three septic shock phenotypes with the dysoxic shock being the most represented.…”

“…In small animals, septic shock is defined as a state of fluidrefractory hypotension requiring vasopressor support and is reportedly associated with higher mortality rates compared to uncomplicated sepsis (3,(12)(13)(14)(15). However, feline septic shock is not commonly investigated (3,15), and the stratification and the prognostic impact of the different septic shock phenotypes based on hyperlactatemia and fluid-refractory hypotension have not yet been documented.…”

Botanicals Reduce Circulating Concentrations of Cholesterol and Triglycerides and Work Synergistically With Arachidonic Acid to Reduce Inflammatory Cytokines in Cats

“…Therefore, foods that have the potential to reduce levels of FLt-3L and subsequently control dendritic cell population might be desirable in certain health conditions in cats. Some of the cytokines including IL-8, and RANTES that have been reduced in cats fed the ARA + botanical extracts have also been reported to be upregulated in cats with sepsis and septic shock ( 29 ) indicating that results from our study have the potential for influencing health conditions in cats with similar upregulation in cytokines. For example, TNFα is a cytokine that is upregulated in diabetic conditions and feline diabetes has been reported ( 30 – 32 ).…”

Characterisation of the serum cytokine profile in feline atopic skin syndrome

“…The observed concentration of each analyte for each sample was calculated using a standard curve generated from the standards and a blank per manufacturer. For each analyte, multiplex data recorded out of range were assigned the respective lowest or highest extrapolated values as described previously; [28][29][30] the values were reported in pg/mL.…”