Therapeutic Modulation of <scp>IL</scp> ‐6/ <scp>STAT</scp> ‐3 and Nitric Oxide by Fenofibrate in Patients With Ulcerative Colitis: A Randomized Controlled Pilot Study

Abstract

BACKGROUND: Peroxisome proliferator-activated receptor α (PPARα) has been reported to exert protective roles in immune-mediated intestinal diseases through inhibition of interleukin-6 (IL-6)-induced signal transducer and activator of transcription factor 3 (STAT3) activation. AIM: To investigate the potential anti-inflammatory effect of fenofibrate, as an add-on therapy to mesalamine, on IL-6/STAT3 and nitric oxide (NO) in patients with ulcerative colitis (UC). METHODS: This pilot, double-blind, randomized, controlled trial included 60 patients diagnosed with mild-to-moderate UC. Patients were randomly allocated into two groups. The placebo group (n = 30) received placebo plus mesalamine 1 g three times daily, and the fenofibrate group (n = 30) received mesalamine 1 g three times daily and fenofibrate 160 mg once daily. The study duration was 6 months. The severity of UC was evaluated using the Disease Activity Index (DAI), and quality of life (QoL) was assessed using the Short Form-36 questionnaire (SF-36). Serum levels of IL-6, NO, C-reactive protein (CRP), and STAT3 were measured for all patients. RESULTS: After treatment, both groups showed a significant reduction in DAI, IL-6, STAT3, NO, and CRP, along with an increase in SF-36 scores. Furthermore, the fenofibrate group demonstrated a significantly greater decrease in DAI (p = 0.0002), IL-6 (p = 0.04), STAT3 (p = 0.004), NO (p = 0.013), and CRP (p = 0.034), as well as a greater increase in SF-36 (p = 0.04) compared with the placebo group. CONCLUSION: Fenofibrate may represent a promising add-on therapy in patients with mild-to-moderate UC by modulating inflammation and improving QoL. TRIAL REGISTRATION: NCT05753267.