Can measurement of chemokines become useful biological and functional markers of early-stage chronic pancreatitis?

Chronic pancreatitis, an irreversible inflammatory disease of the pancreas, is characterized by chronic inflammatory cell infiltration, acinar cell degeneration, and development of fibrosis, which lead to impairment of pancreatic exocrine and endocrine function. Despite marked progress in diagnostic tools and, especially, imaging methods, no consensus has been reached on nomenclature in diagnosis of chronic pancreatitis. A major problem is that no reliable diagnostic test exists for early-stage chronic pancreatitis. The identification of the chemokine system, however, has elucidated the molecular mechanisms of the inflammation contributing to the development of fibrosis in the progression of chronic pancreatitis. Inflammatory chemokines are obviously associated with the chemoattraction of leukocytes in early-stage chronic pancreatitis. Migration of monocytes into the pancreas is one of the earliest events in the formation of pancreatic fibrosis. In particular, monocyte chemoattractant protein-1 (MCP-1) is considered to be a prefibrogenic factor in the progression of chronic pancreatitis. Lately, fractalkine/CX3CL1 is reported to be a membrane-spanning adhesion molecule that can be cleaved from the cell surface to produce a soluble chemoattractant. Our preliminary study showed that serum soluble fractalkine did not correlate with MCP-1 or transforming growth factor beta1 and increased in patients with early-stage chronic pancreatitis. Furthermore, serum soluble fractalkine did not correlate with pancreatic-specific enzymes, such as pancreatic amylase and lipase, and N-benzoyl-L-tyrosyl-p-aminobenzoic acid test results. Therefore, measurement of soluble fractalkine in human serum may be useful as a diagnostic marker of early-stage chronic pancreatitis, and should be considered in future studies, including detailed investigations of soluble fractalkine in patients with chronic pancreatitis.