Severe acute pancreatitis exhibits distinct cytokine signatures and trajectories in humans: a prospective observational study.

Severe acute pancreatitis (SAP) is associated with substantial morbidity and mortality. Several cytokines have been identified to have pathophysiological significance in SAP, but studies characterizing their early trajectories are lacking. Here we characterize the early trajectories of seven key cytokines associated with SAP and compare them with non-SAP subjects. Five proinflammatory cytokines (angiopoietin-2, interleukin-6, interleukin-8, monocyte chemoattractant protein-1, resistin) and two anti-inflammatory cytokines (hepatocyte growth factor, and soluble tumor necrosis factor-α receptor-1A) were measured in a prospective cohort of acute pancreatitis subjects (2012-2016) at the time of enrollment and then every 24 h for 5 days or until discharge. The cytokines' levels and trajectories were calibrated based on date of pain onset and were compared between healthy controls and three severity categories (mild, moderate, and severe). The cohort (n = 170) consisted of 27 healthy controls, 65 mild, 38 moderate, and 40 SAP. From day 1 of symptom onset, SAP subjects exhibited significantly higher levels of both pro- and anti-inflammatory cytokines compared with non-SAP and healthy subjects. But in SAP subjects, all proinflammatory cytokines' levels trended downward after day 2 (except for a flat slope for angiopoeitin-2) whereas for non-SAP subjects, the trajectory was upward: this trajectory difference between SAP versus non-SAP subjects resulted in narrowing of the differences initially seen on day 1 for proinflammatory cytokines. For anti-inflammatory cytokines, the trajectories were uniformly upward for both SAP and non-SAP subjects. Proinflammatory cytokine response is an early and time-sensitive event in SAP that should be accounted for when designing future biomarker studies and/or therapeutic trials.NEW & NOTEWORTHY In this study, we showed that the proinflammatory cytokine response in SAP is an early event, with subsequent downregulation of proinflammatory cytokines beginning at day 1 of symptom onset. Our findings underscore the importance of enrolling subjects very early in the disease course when conducting studies to investigate early immune events of SAP; this current study also serves as an important reference for the design of future biomarker studies and therapeutic trials in SAP.