Limits...
Immune and Inflammatory Responses in GERD and Lansoprazole.

Isomoto H, Nishi Y, Kanazawa Y, Shikuwa S, Mizuta Y, Inoue K, Kohno S - J Clin Biochem Nutr (2007)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Second Department of Internal Medicine, Nagasaki University School of Medicine, 1-7-1 Sakamoto, Nagasaki 852-8501, Japan.

ABSTRACT
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.

No MeSH data available.


Related in: MedlinePlus

Kaplan-Meier analysis: incidence of reflux esophagitis recurrence in patients who had esophageal mucosal interleukin 8 levels that were greater than 10 pg/mg protein (n = 8) or less than 10 pg/mg protein (n = 23). Reprinted with permission [25].
© Copyright Policy - open-access
Related In: Results  -  Collection


getmorefigures.php?uid=PMC2170946&req=5

Figure 3: Kaplan-Meier analysis: incidence of reflux esophagitis recurrence in patients who had esophageal mucosal interleukin 8 levels that were greater than 10 pg/mg protein (n = 8) or less than 10 pg/mg protein (n = 23). Reprinted with permission [25].

Mentions: The elevated levels of IL-8 mRNA and protein levels were significantly decreased after treatment with lansoprazole in RE and NERD patients; these patients had endoscopic healing of the disease and cure of the reflux symptoms, which further highlights the important role of this chemokine in the pathogenesis of GERD [16, 17, 19]. More recently, we conducted a long-term follow-up study dealing with the association of IL-8 protein levels in the esophageal mucosa with RE relapse (Fig. 3) [25]. Thirty-one outpatients with RE, graded according to the LA classification as A or B, not treated with any anti-secretory drugs after healing with 8 weeks of lansoprazole treatment, were enrolled in this study. The estimated RE relapse within 3 years was 75% and 31.3% in patients with IL-8 levels greater than and less than 10 pg/mg protein, respectively. Using Cox’s proportional hazards regression model, RE recurrence was frequently observed in patients who had higher IL-8 levels (>10 pg/mg protein) (odds ratio, 3.5; 95% confidence interval, 1.3–12.8, p<0.01). These preliminary results highlight the fact that mucosal IL-8 levels are an indicator of RE relapse.


Immune and Inflammatory Responses in GERD and Lansoprazole.

Isomoto H, Nishi Y, Kanazawa Y, Shikuwa S, Mizuta Y, Inoue K, Kohno S - J Clin Biochem Nutr (2007)

Kaplan-Meier analysis: incidence of reflux esophagitis recurrence in patients who had esophageal mucosal interleukin 8 levels that were greater than 10 pg/mg protein (n = 8) or less than 10 pg/mg protein (n = 23). Reprinted with permission [25].
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2170946&req=5

Figure 3: Kaplan-Meier analysis: incidence of reflux esophagitis recurrence in patients who had esophageal mucosal interleukin 8 levels that were greater than 10 pg/mg protein (n = 8) or less than 10 pg/mg protein (n = 23). Reprinted with permission [25].
Mentions: The elevated levels of IL-8 mRNA and protein levels were significantly decreased after treatment with lansoprazole in RE and NERD patients; these patients had endoscopic healing of the disease and cure of the reflux symptoms, which further highlights the important role of this chemokine in the pathogenesis of GERD [16, 17, 19]. More recently, we conducted a long-term follow-up study dealing with the association of IL-8 protein levels in the esophageal mucosa with RE relapse (Fig. 3) [25]. Thirty-one outpatients with RE, graded according to the LA classification as A or B, not treated with any anti-secretory drugs after healing with 8 weeks of lansoprazole treatment, were enrolled in this study. The estimated RE relapse within 3 years was 75% and 31.3% in patients with IL-8 levels greater than and less than 10 pg/mg protein, respectively. Using Cox’s proportional hazards regression model, RE recurrence was frequently observed in patients who had higher IL-8 levels (>10 pg/mg protein) (odds ratio, 3.5; 95% confidence interval, 1.3–12.8, p<0.01). These preliminary results highlight the fact that mucosal IL-8 levels are an indicator of RE relapse.

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Second Department of Internal Medicine, Nagasaki University School of Medicine, 1-7-1 Sakamoto, Nagasaki 852-8501, Japan.

ABSTRACT
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.

No MeSH data available.


Related in: MedlinePlus