Cytokine signatures in post-endoscopic retrograde cholangiopancreatography pancreatitis: a pilot study

Jorge D. Machicado; Peter J. Lee; Peter J. Lee; Stacey Culp; Kimberly Stello; Phil A. Hart; Mitchell Ramsey; Adam Lacy-Hulbert; Cate Speake; Zobeida Cruz-Monserrate; B. Joseph Elmunzer; David C. Whitcomb; Georgios I. Papachristou

Authors Jorge D. Machicado, Peter J. Lee, Peter J. Lee, Stacey Culp, Kimberly Stello, Phil A. Hart, Mitchell Ramsey, Adam Lacy-Hulbert, Cate Speake, Zobeida Cruz-Monserrate, B. Joseph Elmunzer, David C. Whitcomb, Georgios I. Papachristou.

Abstract

Background Following endoscopic retrograde cholangiopancreatography (ERCP), post-ERCP pancreatitis (PEP) is the most common complication. The host’s innate immune response to periprocedural pancreatic injury is the hallmark of its pathogenesis. Investigating cytokine signatures associated with PEP and its risk factors can guide understanding of PEP immunopathogenesis.

Methods We conducted a single-center, prospective, observational pilot study in adults at high-risk for PEP. Seven serum cytokines relevant to early acute pancreatitis pathogenesis, angiopoietin-2, hepatocyte growth factor (HGF), interleukin-6 (IL-6), IL-8, monocyte chemotactic protein-1, resistin, and soluble tumor necrosis factor-α receptor 1, were measured in sera collected 2 h pre- and post-ERCP. Levels were compared among healthy controls and ERCP participants who either did or did not develop PEP. Heat maps were constructed to perform a multidimensional exploratory analysis that aimed to determine the cytokine signatures associated with PEP and its participant-related risk factors (female sex, young age, and obesity).

Results A total of 65 participants were enrolled (36 undergoing ERCP and 29 healthy controls). Eight of the 36 (22.2%) ERCP participants developed PEP. Baseline IL-8 levels measured before ERCP were elevated in participants who developed PEP (7.5 vs. 14.8 pg/mL, P=0.02), and most strongly upregulated in women under 40 years of age. HGF levels post-ERCP were higher in participants with PEP (738.0 vs. 556.6 pg/mL, P=0.04), and most strongly upregulated in obese participants.

Conclusions Pre-ERCP IL-8 and post-ERCP HGF are associated with the development of PEP. Findings from this pilot study can inform the design of translational work in the immunopathogenesis of PEP.

Keywords Acute pancreatitis, endoscopic retrograde cholangiopancreatography, post-ERCP pancreatitis, pathogenesis

Ann Gastroenterol 2024; 37 (6): 734-741