Immune and Inflammatory Responses in GERD and Lansoprazole.
The exact pathophysiological mechanisms responsible for gastroesophageal reflux disease (GERD) remain unclear. Recent studies have shown that mucosal immune and inflammatory responses, characterized by specific cytokine and chemokine profiles, may underlie the diverse esophageal phenotypes of GERD. Interleukin 8 (IL-8), a representative chemokine, mediates neutrophil trafficking via its receptors, mainly CXCR-1. The IL-8 mRNA and protein levels are increased in the esophageal mucosa, not only in reflux esophagitis (RE), but also in endoscopy-negative GERD (NERD), through activation of nuclear factor-kappaB (NF-kappaB), which is a pivotal transcription factor. Mucosal IL-8 concentrations have been found to parallel the endoscopic severity of RE, implying that this cytokine is a key player in the development of GERD. The mucosal levels of the C-C chemokines, macrophage chemoattractant protein 1 (MCP-1) and regulated on activation normal T-cell-expressed and presumably secreted (RANTES), which primarily attract monocytes and lymphocytes to the site of inflammation, respectively, are also elevated in RE. The secreted levels of IL-8 and IL-1beta, a prototype of proinflammatory cytokine, are maximal at the proximal segment within Barrett esophagus (BE) tissue. The expression of the two pleiotrophic proinflammatory cytokines, IL-6 and tumor necrosis factor alpha, is enhanced in the intestinal epithelium of BE, which places this epithelium at a higher risk for developing malignancy. BE is characterized by a distinct Th-2 predominant cytokine profile (IL-4 and -10), compared to the proinflammatory nature of RE (interferone-gamma). Treatment with a proton pump inhibitor, lansoprazole reduces the mucosal levels of IL-8 mRNA and protein in GERD, including RE and NERD. This may occur in part through an anti-inflammatory action of proton pump inhibitors beyond gastric acid inhibition.
Isomoto
Hajime
H
Second Department of Internal Medicine, Nagasaki University School of Medicine, 1-7-1 Sakamoto, Nagasaki 852-8501, Japan.
Nishi
Yoshito
Y
Kanazawa
Yusei
Y
Shikuwa
Saburo
S
Mizuta
Yohei
Y
Inoue
Kenichiro
K
Kohno
Shigeru
S