Elevated Serum Fibroblast Growth Factor 21 in Humans with Acute Pancreatitis

Abstract

Background: The metabolic regulator Fibroblast Growth Factor 21 (FGF21) is highly expressed in the acinar pancreas, but its role in pancreatic function is obscure. It appears to play a protective role in acute experimental pancreatitis in mice. The aim of this study was to define an association between FGF21 and the course and resolution of acute pancreatitis in humans.

Methods and principal findings: Twenty five subjects with acute pancreatitis admitted from May to September 2012 to the Beth Israel Deaconess Medical Center (BIDMC) were analyzed. Serial serum samples were collected throughout hospitalization and analyzed for FGF21 levels by ELISA. Twenty healthy subjects sampled three times over a four week period were used as controls. We found that, in patients with pancreatitis, serum FGF21 rises significantly and peaks four to six days after the maximum lipase level, before slowly declining. Maximum FGF21 levels were significantly greater than baseline levels for acute pancreatitis subjects (1733 vs. 638 pg/mL, P = 0.003). This maximum value was significantly greater than the highest value observed for our control subjects (1733 vs. 322 pg/mL, P = 0.0002). The ratio of active to total FGF21 did not change during the course of the disease (42.5% vs. 44.4%, P = 0.58). Fold increases in FGF21 were significantly greater in acute pancreatitis subjects than the fold difference seen in healthy subjects (4.7 vs. 2.0, P = 0.01). Higher fold changes were also seen in severe compared to mild pancreatitis (18.2 vs. 4.4, P = 0.01). The timing of maximum FGF21 levels correlated with day of successful return to oral intake (R2 = 0.21, P = 0.04).

Conclusions: Our results demonstrate that serum FGF21 rises significantly in humans with acute pancreatitis. The pancreas may be contributing to increased FGF21 levels following injury and FGF21 may play a role in the recovery process.

Fig 1. FGF21 and lipase levels in acute pancreatitis subjects and FGF21 levels in control subjects.

Panel A shows mean serum FGF21 and lipase levels in acute pancreatitis subjects from the day of onset of symptoms, while panel B shows mean FGF21 levels in healthy control subjects drawn every two weeks over the course of four weeks. Data shown as the mean ± SEM.

Fig 2. Maximum FGF21 levels in acute pancreatitis are significantly greater than baseline levels and control levels.

The baseline FGF21 level for acute pancreatitis subjects is the lower value of either the first or last measured FGF21 level during a hospital course. Data shown as mean ± SEM. N = 25 for acute pancreatitis, N = 20 for control subjects. ** P < 0.01 compared to maximum levels; *** P < 0.001 compared to maximum levels; **** P < 0.0001 compared to maximum levels.