Serum Cytokine Profiling in Cats with Acute Idiopathic Cystitis

Abstract

BackgroundFeline idiopathic cystitis (FIC) is a common lower urinary tract disorder of domestic cats that resembles interstitial cystitis/painful bladder syndrome (IC/PBS) in humans. Diagnosis of FIC is based on clinical signs and exclusion of other disorders because of a lack of specific pathologic findings or other objective biomarkers. Cytokines are potential noninvasive biomarkers to define the presence, severity, and progression of disease, and response to treatment.ObjectivesThe objective of this pilot study was to determine concentrations of selected cytokines in serum from healthy cats and cats with acute FIC.AnimalsSerum samples from 13 healthy cats and from 12 cats with nonobstructive acute FIC were utilized.MethodsMultiplex analysis of 19 cytokines (CCL2, CCL5, CXCL1, CXCL12, CXCL8, Flt3L, GM‐CSF, IFN‐γ, IL‐12 (p40), IL‐13, IL‐18, IL‐1β, IL‐2, IL‐4, IL‐6, PDGF‐BB, SCF, sFas, and TNF‐α) was performed with a commercially available feline‐specific multiplex bead‐based assay.ResultsMean serum concentrations of IL‐12 (p40; P < 0.0001), CXCL12 (P = 0.002), IL‐18 (P = 0.032), and Flt3L (P = 0.0024) were significantly increased in FIC cats compared to healthy cats. GM‐CSF, IL‐1b, IL‐2, and PDGF‐BB were undetectable or detected in an insufficient number of cats to allow meaningful comparisons.Conclusions and Clinical ImportanceWe have identified increased serum concentrations of pro‐inflammatory cytokines and chemokines CXCL12, IL‐12, IL‐18, and Flt3L in FIC‐affected cats. These findings suggest potential candidates for noninvasive biomarkers for diagnosis, staging, and therapeutic outcome monitoring of affected cats and provide additional insight into the etiopathogenesis of FIC.

Cytokine and Chemokine Profiling in Cats With Sepsis and Septic Shock

“…For cytokine measurements, citrated plasma was generated by centrifugation of whole blood for 10 min at 1,370 g. After centrifugation, plasma was frozen at −80 • C until cytokine analyses were performed. An antibody-coated microspherebased multiplex feline-specific cytokine immunoassay kit (Milliplex MAP Feline Cytokine/Chemokine Magnetic Bead Panel, Millipore-Sigma, Billerica, MA) was used to measure 19 cytokines as previously described (19)(20)(21)(22). Analytes included in the kit were Fas, FMS-like tyrosine kinase-3 ligand (Flt-3L), granulocyte macrophage-colony stimulating factor (GM-CSF), interferon-γ (IFN-γ), interleukin 1beta (IL-1β), IL-2, plateletderived growth factor-BB (PDGF-BB), IL-12, IL-13, IL-4, IL-6, IL-8, keratinocyte chemoattractant-like (KC-like), stromal cellderived factor 1 (SDF-1), Regulated upon Activation, Normal T cell Expressed, and Secreted (RANTES), stem cell factor (SCF), C-C motif chemokine ligand-2 (CCL-2) [also known as monocyte chemoattractant protein-1 (MCP-1)], tumor-necrosis factor-α (TNF-α), and IL-18.…”

“…Multiplex assays are able to simultaneously and rapidly measure a wide variety of immunologically active proteins in small volumes of biological samples. Feline-specific multiplex assays have recently been used to measure cytokines in serum and plasma samples from cats affected by heterogeneous diseases, idiopathic cystitis and degenerative joint disease (19)(20)(21)(22), and demonstrate reliable cytokine detection when the blood concentration of the analytes is high.…”

Clinical-diagnostic criteria and peculiarities of treatment of urocystitis in cats

“…Positive/negative or double contrast roentgenograpy and ultrasonography of the abdominal organs allow a detailed study of the bladder to diagnose urocystitis by measuring the thickness of the bladder wall, detecting stones, blood clots, bladder rupture, neoplasia, dislocation and diverticulum (Farrow, 2003;Hostutler et al, 2005;Kealy et al, 2011). The use of cytokines as potentially non-invasive biomarkers for the diagnosis and determination of the effectiveness of treatment of idiopathic urocystitis in cats is suggested (Parys et al, 2018). There is an announcement that the use of immunostimulants of bacterial origin are best suited for treatment of this pathology, in particular Uro-Vaxom ® , as one of its mechanisms of action is the formation of specific immunoglobulins and activation of cellular immunity (Semyonov et al, 2015).…”

Cytokine and Chemokine Concentrations as Biomarkers of Feline Mycobacteriosis

“…Cytokine profiling in companion animal medicine has been the subject of a number of recent studies 62 , 64 , 65 . One limitation of such studies to date is the study design to compare cytokine profiles in animals with the designated diagnosis of interest and apparently healthy animals as controls.…”

“…For example; CXCL10 and CCL2 plasma concentrations can be combined with circulating levels of IFN-γ to more accurately discriminate between active and latent TB states, whilst the quantification of vascular endothelial growth factor can help differentiate patients with TB pleural effusion from those with neoplastic pleural effusions 57 , 61 . Similar assays have also been used successfully in the study of a limited number of companion animal diseases, including canine lymphoma and feline cystitis 62 – 65 .…”