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Martin Bluth, MD, PhD; Yin-yao Lin, PhD; Hong Zhang, PhD; Domenico Viterbo, PhD; Michael Zenilman, MD

Arch Surg. 2008;143(3):227-233.

Hypothesis  Blood leukocytes play a major role in mediating local and systemic inflammation during acute pancreatitis. We hypothesize that peripheral blood mononuclear cells (PBMCs) in circulation exhibit unique changes in gene expression and could provide a "reporter" function that reflects the inflammatory response in the pancreas with acute pancreatitis.

Design  To determine specific changes in blood leukocytes during acute pancreatitis, we studied the gene transcription profile in PBMCs in a rat model of experimental pancreatitis (sodium taurocholate). Normal rats, saline controls, and a model of septic shock were used as a controls. Complementary RNA obtained from PBMCs of each group (n = 3 in each group) were applied to Affymetrix rat genome DNA GeneChip arrays.

Main Outcome Measure  Changes in gene expression.

Results  From the 8799 rat genes analyzed, 140 genes showed unique significant changes in their expression in PBMCs during the acute phase of pancreatitis, but not in sepsis. Among the 140 genes, 57 were up-regulated, while 69 were down-regulated. Platelet-derived growth factor receptor, prostaglandin E₂ receptor, and phospholipase D₁ were among the top up-regulated genes. Others included genes involved in G protein–coupled receptor and transforming growth factor β–mediated signaling pathways, while genes associated with apoptosis, glucocorticoid receptors, and even the cholecystokinin receptor were down-regulated.

Conclusions  Microarray analysis in transcriptional profiling of PBMCs showed that genes that are uniquely related to molecular and pancreatic function display differential expression in acute pancreatitis. Profiling genes obtained from an easily accessible source during severe pancreatitis may identify surrogate markers for disease severity.

Author Affiliations: Department of Surgery, State University of New York Downstate Medical Center, Brooklyn.

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