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

BACKGROUND: Severe acute pancreatitis (SAP) is associated with substantial morbidity and mortality. Several cytokines have been identified to have pathophysiologic significance in SAP, but studies characterizing their early trajectories are lacking.

AIM: Characterize the early trajectories of seven key cytokines associated with SAP and compare them to non-SAP subjects.

METHODS: Five pro-inflammatory 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 at the time of enrollment and then every 24-hours for five days or until discharge. The cytokines' levels and trajectories were calibrated based on date of pain onset and were compared between healthy controls, and 3 severity categories (mild, moderate and severe).

RESULTS: 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 to non-SAP and healthy subjects. But in SAP subjects, all pro-inflammatory 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 vs non-SAP subjects resulted in narrowing of the differences initially seen on day 1 for pro-inflammatory cytokines. For anti-inflammatory cytokines, the trajectories were uniformly upward for both SAP and non-SAP subjects.

CONCLUSIONS: Pro-inflammatory cytokine response is an early event in SAP which should be accounted for when designing biomarker studies and/or therapeutic trials.