Increased Gene Expression of Circulating Pro‐inflammatory Cytokines in Felines with Idiopathic Cystitis

Abstract

Feline idiopathic cystitis (FIC) is one of the common urinary disorders of domestic cats. Inflammation is a key characteristic in the pathogenesis of cystitis and pro-inflammatory cytokines and chemokines have been hypothesized to contribute to the progression of cystitis. Several cytokines have been reported in the urine and bladder in animal models of cystitis and in humans. Circulating levels of cytokines and chemokines are important biomarkers to assess the presence and severity of FIC and may also be useful as a response variable to assess dietary intervention. We assessed the circulating inflammatory markers in a retrospective study in cats with cystitis (n=6; 9.2-18.6 yr) from blood samples collected at necropsy, as well as in control cats (n=6; 5.9-14.6 yr). While most cats had been diagnosed with idiopathic cystitis during their life-time, two cats also were diagnosed with urinary tract infection. End-of-life pathology reports indicated inflammation and presence of inflammatory infiltrates in the bladder (lamina propria) with some cats also showing renal inflammation. RNA was extracted from blood samples, and we assessed the circulating levels of inflammatory genes using ThermoFisher Scientific Custom TaqMan array plates that were feline-specific, in the blood of cats obtained at the end-of-life. Data were analyzed using the using the ΔΔCt method using HPRT as the housekeeping gene. The levels of circulating mRNA that were increased greater than 1.5-fold in the FIC cats, when compared to controls, included interleukin-4 (>1.96-fold), interleukin-1b (>1.75), bone morphogenetic protein -2 (>1.74), interleukin-8 (CXCL8; >1.73), interleukin-16 (>1.7), and CSF-1 (>1.58). While IL-4 may have some anti-inflammatory effects, an increase in IL-4 can also lead to T-cell proliferation and increased inflammation. An increase in IL-16, a chemoattractant and activator of T-cells, as well as IL-8, indicates an important role of T-cell activation in the pathogenesis and progression of cystitis. Our results identify elevated levels of several pro-inflammatory molecules that may be potential targets for alleviating chronic inflammation associated with cystitis. Nutritional intervention to reduce the levels of selected inflammatory cytokines may be useful in the management of cystitis