Evaluation of serum cytokines in cats with and without degenerative joint disease and associated pain

Abstract

Degenerative joint disease is common in cats, with signs of pain frequently found on orthopedic examination and radiographs often showing evidence of disease. However, understanding of the pathophysiology of degenerative joint disease and associated pain remains limited. Several cytokines have been identified as having a role in pain in humans, but this has not been investigated in cats. The present study was performed to use a multiplex platform to evaluate the concentration of 19 cytokines and chemokines in serum samples obtained from cats with and without degenerative joint disease and associated pain. Samples from a total of 186 cats were analyzed, with cats representing a range of severity on radiographic and orthopedic evaluations and categorized by degenerative joint disease scores and pain scores. Results showed that cats with higher radiographic degenerative joint disease scores have higher serum concentrations of IL-4 and IL-8, while cats with higher orthopedic exam pain scores have higher concentrations of IL-8, IL-2, and TNF-α increased concentration of IL-8 in degenerative joint disease and pain may be confounded by the association with age. Discriminant analysis was unable to identify one or more cytokines that distinguish between groups of cats classified based on degenerative joint disease score category or pain score category. Finally, cluster analysis driven by analyte concentrations show separation of groups of cats, but features defining the groups remain unknown. Further studies are warranted to investigate any changes in cytokine concentrations in response to analgesic therapies, and further evaluate the elevations in cytokine concentrations found here, particularly focused on studies of local cytokines present in synovial fluid.

Cytokine and Chemokine Profiling in Cats With Sepsis and Septic Shock

“…This inevitably limited our evaluation of the utility of these markers and may warrant reassessment of the utility of the full 19-plex assay in cats. As the present study involved an exploratory analysis of cytokines in feline sepsis it was desirable to measure the maximum number of cytokines, similar to other exploratory studies in related fields (20,48). Additionally, there was no clear difference between healthy controls and sick cats (sepsis and septic shock) for the majority of the investigated analytes.…”

“…IL-8 has received attention as a marker of sepsis and bacteremia in people (26,27,34) and it may be a useful marker in dogs with polyarthritis, sepsis and trauma (13,35,36). Its specificity for sepsis is not known in cats, but increased IL-8 concentrations have been documented in the course of sterile inflammatory diseases like feline idiopathic cystitis and degenerative joint disease (20,22).…”

“…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.…”

Bronchoalveolar lavage hemosiderosis in dogs and cats with respiratory disease

“…Primary hemostatic disorders could manifest with hemarthrosis and pulmonary bleeding, or nonsteroidal anti‐inflammatory drug therapy could induce hemorrhage of joints and lungs . Alternatively, increased circulating inflammatory cytokines secondary to osteoarthrosis could affect pulmonary vascular function . A complete history of nonsteroidal anti‐inflammatory use and the temporal association with the time of the BAL procedures was inconsistently recorded, and patients receiving this medication did not undergo hemostatic testing.…”