Mucosal concentrations of proinflammatory cytokines and chemokines at gastric cardia: implication of Helicobacter pylori infection and gastroesophageal reflux.
OBJECTIVE
The pathogenesis of carditis remains unclear, although gastroesophageal reflux disease (GERD) and Helicobacter pylori infection have been proposed. Little is known about the profile of proinflammatory cytokines and chemokines in the pathogenesis of carditis.


METHODS
We studied 28 patients with GERD and 40 controls. Two biopsy specimens were taken endoscopically from the cardiac mucosa within 5 mm from the squamocolumnar junction; one was snap frozen for measurement of mucosal levels of interleukin 1beta (IL-1beta), tumor necrosis factor-alpha, IL-6, IL-8, monocyte chemoattractant protein 1 (MCP-1), regulated on activation normal T-cell expressed and presumably secreted (RANTES) by enzyme-linked immunosorbent assays, while another was processed for histopathology. H. pylori infection was assessed by serology, rapid urease test, and histology with Giemsa staining. Samples were taken from the cardia of 18 H. pylori-positive patients, before and after eradication treatment.


RESULTS
Carditis was significantly associated with H. pylori infection, but not GERD. IL-8, MCP-1, and RANTES levels were significantly higher in cardiac mucosa of patients with carditis than in those without it and in patients with than without H. pylori infection. IL-8 concentrations were significantly associated with the degree of neutrophil infiltration within the cardiac mucosa and decreased after cure of the infection. Mucosal MCP-1 and RANTES levels correlated positively with the grades of mononuclear cell infiltration and IL-1beta concentrations.


CONCLUSIONS
Our results indicate that chemokines produced locally in the cardiac mucosa may be involved in the development of H. pylori-associated carditis.
Isomoto
Hajime
H
Department of Endoscopy, Nagasaki University School of Medicine, Nagasaki, Japan.
Nishi
Yoshito
Y
Wang
Aiping
A
Takeshima
Fuminao
F
Omagari
Katsuhisa
K
Mizuta
Yohei
Y
Shikuwa
Saburo
S
Murata
Ikuo
I
Kohno
Shigeru
S
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002299:Cardia / Q000378:metabolism*; D016022:Case-Control Studies; D018946:Chemokine CCL5 / Q000378:metabolism; D018925:Chemokines / Q000032:analysis / Q000378:metabolism; D016207:Cytokines / Q000032:analysis / Q000378:metabolism*; D005260:Female; D005753:Gastric Mucosa / Q000737:chemistry* / Q000378:metabolism; D005764:Gastroesophageal Reflux / Q000175:diagnosis* / Q000378:metabolism; D016481:Helicobacter Infections / Q000175:diagnosis* / Q000378:metabolism; D016480:Helicobacter pylori / Q000302:isolation & purification; D006801:Humans; D018836:Inflammation Mediators / Q000032:analysis; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011336:Probability; D011379:Prognosis; D018570:Risk Assessment; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index; D018709:Statistics, Nonparametric
D018946:Chemokine CCL5; D018925:Chemokines; D016207:Cytokines; D018836:Inflammation Mediators