ABSTRACT
BACKGROUND: Feline 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. OBJECTIVES: The objective of this pilot study was to determine concentrations of selected cytokines in serum from healthy cats and cats with acute FIC. ANIMALS: Serum samples from 13 healthy cats and from 12 cats with nonobstructive acute FIC were utilized. METHODS: Multiplex analysis of 19 cytokines (CCL2, CCL5, CXCL1, CXCL12, CXCL8, Flt3L, GM-CSF, IFN-γ, IL-12 (p40), IL-13, IL-18, IL-1ß, 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. RESULTS: Mean 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 IMPORTANCE: We 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.
Subject(s)
Cat Diseases/blood , Cystitis/veterinary , Cytokines/blood , Acute Disease , Animals , Biomarkers/blood , Case-Control Studies , Cat Diseases/diagnosis , Cats , Chemokine CXCL12/blood , Chemokines, CC/blood , Cystitis/blood , Cystitis/diagnosis , Female , Interferon-gamma/blood , Interleukin-12/blood , Interleukin-18/blood , Interleukins/blood , Male , Pilot Projects , Retrospective Studies , Tumor Necrosis Factor-alpha/bloodABSTRACT
BACKGROUND: Chronic inflammatory diseases are common in cats and mesenchymal stem cells (MSC) are a promising therapeutic approach for management of these disorders. The purpose of this study was to evaluate the safety of intraperitoneal injection of MSC in cats. HYPOTHESIS: Intrapertioneal injection of autologous MSC in cats is safe. ANIMALS: Ten healthy adult purpose-bred cats. METHODS: Mesenchymal stem cells were isolated from subcutaneous adipose tissue collected during ovariohysterectomy and characterized for expression of CD90, CD105 and CD44 and trilineage differentiation. Three weeks postoperatively a complete blood count, serum chemistry profile, urinalysis, and abdominal ultrasound were performed. Five cats then received 1 × 10(6) of autologous MSC/kg of body weight intraperitoneally with ultrasound guidance; 5 additional cats were sham injected. Cats were monitored for 6 weeks with daily physical examinations and weekly clinicopathological evaluations. Abdominal ultrasonography was repeated at weeks 1 and 5 after injection. RESULTS: Serious adverse effects were not observed in any MSC-injected cat. Two animals developed transient lethargy and decreased activity. Jejunal lymph node size was increased in MSC-injected cats compared to controls at weeks 1 (1.38 ± 0.25 versus 0.88 ± 0.25 cm(2); P = .036) and 5 (1.75 ± 0.82 versus 0.79 ± 0.12 cm(2); P = .047). A hyperechoic renal segmental cortical lesion was observed in 1 MSC-injected cat. CONCLUSIONS AND CLINICAL RELEVANCE: Intraperitoneal MSC injection was well tolerated with only mild, self-limiting adverse effects being observed in 2 cats. This route provides a safe means of administration for cell-based treatment in cats.