Indomethacin down-regulating HMGB1 and TNF-α to prevent pancreatitis after endoscopic retrograde cholangiopancreatography

Abstract

Background and aims: Several articles demonstrated that non-steroidal anti-inflammation drugs (NSAIDs) were effective in reducing the incidence of pancreatitis after endoscopic retrograde cholangiopancreatography (PEP). However, studies revealed inconsistent results. The mechanism of NSAIDs in preventing PEP is still little known. Therefore, the aim of our study was to evaluate the efficacy of NSAIDs for PEP prophylaxis and further to explore the mechanism of NSAIDs for prevention of PEP.Methods: Patients who underwent endoscopic retrograde cholangiopancreatography (ERCP) were randomly assigned to receive 100 mg rectal indomethacin or glycerin suppository 15–20 min before ERCP. The primary outcome was the rate of PEP. And the levels of serum HMGB1 and TNF-α were also measured before ERCP and 3 and 24 h after ERCP. Univariate analysis and multivariate analysis were carried out to estimate the independent risk factors for PEP.Results: Totally, 100 patients were enrolled, 50 received indomethacin and 50 with placebo (glycerin suppository). PEP developed in six patients in indomethacin group and 16 in the control group, the difference was significant (p = .016). The levels of HMGB1 and TNF-α were significantly decreased in indomethacin group at 3 (p < .0001) and 24 h (p < .0001) after ERCP, compared to the control group. Multivariate analysis revealed that duration of ERCP (OR, 0.221; 95% CI, 0.072–0.680; p = .008) and usage of NSAIDs (OR, 0.278; 95% CI, 0.090–0.861; p = .026) were independent predictors of PEP.Conclusions: Rectal indomethacin could significantly reduce the risk of PEP by down-regulating the levels of HMGB1 and TNF-α.