Previous Article | Next Article 
Infection and Immunity, December 1998, p. 5964-5971, Vol. 66, No. 12
0019-9567/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.
Local Cytokine Response in Helicobacter
pylori-Infected Subjects
C.
Lindholm,1,*
M.
Quiding-Järbrink,1
H.
Lönroth,2
A.
Hamlet,1 and
A.-M.
Svennerholm1
Department of Medical Microbiology and
Immunology, Göteborg University,1 and
Department of Surgery, Sahlgrenska University
Hospital,2 Göteborg, Sweden
Received 24 April 1998/Returned for modification 15 July
1998/Accepted 17 September 1998
The host immune response to Helicobacter pylori
infection might be of importance with regard to the outcome of
infection by this organism, e.g., to explain why only a proportion of
infected subjects develop peptic ulcers. In this study we have analyzed the local response of different cytokines
i.e., the proinflammatory interleukin-1
, (IL-1
), IL-6, tumor necrosis factor alpha, and IL-8; the immunoregulatory gamma interferon (IFN-
); and IL-4; and
the anti-inflammatory transforming growth factor beta (TGF-
)
in antral biopsy specimens from H. pylori-infected
duodenal ulcer (DU) patients and asymptomatic (AS) carriers (i.e., with
chronic gastritis only). For comparison, biopsy specimens from
uninfected healthy individuals were also analyzed. An
immunohistochemical technique was used to allow quantification of the
cytokine responses as well as identification of the cell types
associated with the cytokine expression. We found that the levels of
all of the studied cytokines except IL-4 were increased in the
H. pylori-infected subjects compared to the levels in
the healthy individuals. Our results indicate that the antral cytokine
response is of the Th1 type since IFN-
, but not
IL-4, was up-regulated both in H. pylori-infected DU patients and in AS carriers. However, there were no significant differences in either proinflammatory or immunoregulatory cytokine levels when H. pylori-infected subjects with and
without peptic ulcers were compared. Some of the cytokines,
particularly IL-1
and TGF-
, were also found in the gastric
mucosae of healthy, uninfected subjects. We also showed that the
gastric epithelium contributes substantially to the antral cytokine
response of the proinflammatory cytokines IL-1
and IL-6 in
addition to IL-8.
*
Corresponding author. Mailing address: Department of
Medical Microbiology and Immunology, Göteborg University,
Guldhedsgatan 10A, S-413 46 Göteborg, Sweden. Phone: 46 31 342 62 16. Fax: 46 31 82 69 76. E-mail:
catharina.lindholm{at}microbio.gu.se.
Infection and Immunity, December 1998, p. 5964-5971, Vol. 66, No. 12
0019-9567/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.
This article has been cited by other articles:
-
Algood, H. M. S., Allen, S. S., Washington, M. K., Peek, R. M. Jr., Miller, G. G., Cover, T. L.
(2009). Regulation of Gastric B Cell Recruitment Is Dependent on IL-17 Receptor A Signaling in a Model of Chronic Bacterial Infection. J. Immunol.
183: 5837-5846
[Abstract]
[Full Text]
-
Benoit, B. N., Kobayashi, M., Kawakubo, M., Takeoka, M., Sano, K., Zou, J., Itano, N., Tsutsui, H., Noda, T., Fukuda, M., Nakayama, J., Taniguchi, S.
(2009). Role of ASC in the Mouse Model of Helicobacter pylori Infection. J. Histochem. Cytochem.
57: 327-338
[Abstract]
[Full Text]
-
Robinson, K, Kenefeck, R, Pidgeon, E L, Shakib, S, Patel, S, Polson, R J, Zaitoun, A M, Atherton, J C
(2008). Helicobacter pylori-induced peptic ulcer disease is associated with inadequate regulatory T cell responses. Gut
57: 1375-1385
[Abstract]
[Full Text]
-
Mahajan, R., El-Omar, E. M., Lissowska, J., Grillo, P., Rabkin, C. S., Baccarelli, A., Yeager, M., Sobin, L. H., Zatonski, W., Channock, S. J., Chow, W.-H., Hou, L.
(2008). Genetic Variants in T Helper Cell Type 1, 2 and 3 Pathways and Gastric Cancer Risk in a Polish Population. Jpn J Clin Oncol
38: 626-633
[Abstract]
[Full Text]
-
Yamaoka, T., Yan, F., Cao, H., Hobbs, S. S., Dise, R. S., Tong, W., Polk, D. B.
(2008). Transactivation of EGF receptor and ErbB2 protects intestinal epithelial cells from TNF-induced apoptosis. Proc. Natl. Acad. Sci. USA
105: 11772-11777
[Abstract]
[Full Text]
-
Hisatsune, J., Nakayama, M., Isomoto, H., Kurazono, H., Mukaida, N., Mukhopadhyay, A. K., Azuma, T., Yamaoka, Y., Sap, J., Yamasaki, E., Yahiro, K., Moss, J., Hirayama, T.
(2008). Molecular Characterization of Helicobacter pylori VacA Induction of IL-8 in U937 Cells Reveals a Prominent Role for p38MAPK in Activating Transcription Factor-2, cAMP Response Element Binding Protein, and NF-{kappa}B Activation. J. Immunol.
180: 5017-5027
[Abstract]
[Full Text]
-
Beswick, E. J., Pinchuk, I. V., Das, S., Powell, D. W., Reyes, V. E.
(2007). Expression of the Programmed Death Ligand 1, B7-H1, on Gastric Epithelial Cells after Helicobacter pylori Exposure Promotes Development of CD4+ CD25+ FoxP3+ Regulatory T Cells. Infect. Immun.
75: 4334-4341
[Abstract]
[Full Text]
-
Wu, Y.-Y., Tsai, H.-F., Lin, W.-C., Hsu, P.-I, Shun, C.-T., Wu, M.-S., Hsu, P.-N.
(2007). Upregulation of CCL20 and Recruitment of CCR6+ Gastric Infiltrating Lymphocytes in Helicobacter pylori Gastritis. Infect. Immun.
75: 4357-4363
[Abstract]
[Full Text]
-
Kundu, P., Mukhopadhyay, A. K., Patra, R., Banerjee, A., Berg, D. E., Swarnakar, S.
(2006). Cag Pathogenicity Island-independent Up-regulation of Matrix Metalloproteinases-9 and -2 Secretion and Expression in Mice by Helicobacter pylori Infection. J. Biol. Chem.
281: 34651-34662
[Abstract]
[Full Text]
-
Algood, H. M. S., Cover, T. L.
(2006). Helicobacter pylori Persistence: an Overview of Interactions between H. pylori and Host Immune Defenses. Clin. Microbiol. Rev.
19: 597-613
[Abstract]
[Full Text]
-
Ellmark, P., Ingvarsson, J., Carlsson, A., Lundin, B. S., Wingren, C., Borrebaeck, C. A. K.
(2006). Identification of Protein Expression Signatures Associated with Helicobacter pylori Infection and Gastric Adenocarcinoma Using Recombinant Antibody Microarrays. Mol. Cell. Proteomics
5: 1638-1646
[Abstract]
[Full Text]
-
Kusters, J. G., van Vliet, A. H. M., Kuipers, E. J.
(2006). Pathogenesis of Helicobacter pylori Infection. Clin. Microbiol. Rev.
19: 449-490
[Abstract]
[Full Text]
-
Kaparakis, M., Laurie, K. L., Wijburg, O., Pedersen, J., Pearse, M., van Driel, I. R., Gleeson, P. A., Strugnell, R. A.
(2006). CD4+ CD25+ Regulatory T Cells Modulate the T-Cell and Antibody Responses in Helicobacter-Infected BALB/c Mice.. Infect. Immun.
74: 3519-3529
[Abstract]
[Full Text]
-
Das, S., Suarez, G., Beswick, E. J., Sierra, J. C., Graham, D. Y., Reyes, V. E.
(2006). Expression of B7-H1 on Gastric Epithelial Cells: Its Potential Role in Regulating T Cells during Helicobacter pylori Infection.. J. Immunol.
176: 3000-3009
[Abstract]
[Full Text]
-
Bjorstad, A., Fu, H., Karlsson, A., Dahlgren, C., Bylund, J.
(2005). Interleukin-8-Derived Peptide Has Antibacterial Activity. Antimicrob. Agents Chemother.
49: 3889-3895
[Abstract]
[Full Text]
-
Lundgren, A., Trollmo, C., Edebo, A., Svennerholm, A.-M., Lundin, B. S.
(2005). Helicobacter pylori-Specific CD4+ T Cells Home to and Accumulate in the Human Helicobacter pylori-Infected Gastric Mucosa. Infect. Immun.
73: 5612-5619
[Abstract]
[Full Text]
-
Mueller, A., O'Rourke, J., Chu, P., Chu, A., Dixon, M. F., Bouley, D. M., Lee, A., Falkow, S.
(2005). The Role of Antigenic Drive and Tumor-Infiltrating Accessory Cells in the Pathogenesis of Helicobacter-Induced Mucosa-Associated Lymphoid Tissue Lymphoma. Am. J. Pathol.
167: 797-812
[Abstract]
[Full Text]
-
Lopes, A. I., Quiding-Jarbrink, M., Palha, A., Ruivo, J., Monteiro, L., Oleastro, M., Santos, A., Fernandes, A.
(2005). Cytokine Expression in Pediatric Helicobacter pylori Infection. CVI
12: 994-1002
[Abstract]
[Full Text]
-
Navaglia, F, Basso, D, Zambon, C-F, Ponzano, E, Caenazzo, L, Gallo, N, Falda, A, Belluco, C, Fogar, P, Greco, E, Di Mario, F, Rugge, M, Plebani, M
(2005). Interleukin 12 gene polymorphisms enhance gastric cancer risk in H pylori infected individuals. J. Med. Genet.
42: 503-510
[Full Text]
-
Oh, J. D., Karam, S. M., Gordon, J. I.
(2005). Intracellular Helicobacter pylori in gastric epithelial progenitors. Proc. Natl. Acad. Sci. USA
102: 5186-5191
[Abstract]
[Full Text]
-
Yamaoka, Y., Yamauchi, K., Ota, H., Sugiyama, A., Ishizone, S., Graham, D. Y., Maruta, F., Murakami, M., Katsuyama, T.
(2005). Natural History of Gastric Mucosal Cytokine Expression in Helicobacter pylori Gastritis in Mongolian Gerbils. Infect. Immun.
73: 2205-2212
[Abstract]
[Full Text]
-
Enarsson, K., Brisslert, M., Backert, S., Quiding-Jarbrink, M.
(2005). Helicobacter pylori Induces Transendothelial Migration of Activated Memory T Cells. Infect. Immun.
73: 761-769
[Abstract]
[Full Text]
-
Lundgren, A., Stromberg, E., Sjoling, A., Lindholm, C., Enarsson, K., Edebo, A., Johnsson, E., Suri-Payer, E., Larsson, P., Rudin, A., Svennerholm, A.-M., Lundin, B. S.
(2005). Mucosal FOXP3-Expressing CD4+ CD25high Regulatory T Cells in Helicobacter pylori-Infected Patients. Infect. Immun.
73: 523-531
[Abstract]
[Full Text]
-
Kranzer, K., Eckhardt, A., Aigner, M., Knoll, G., Deml, L., Speth, C., Lehn, N., Rehli, M., Schneider-Brachert, W.
(2004). Induction of Maturation and Cytokine Release of Human Dendritic Cells by Helicobacter pylori. Infect. Immun.
72: 4416-4423
[Abstract]
[Full Text]
-
Galgani, M., Busiello, I., Censini, S., Zappacosta, S., Racioppi, L., Zarrilli, R.
(2004). Helicobacter pylori Induces Apoptosis of Human Monocytes but Not Monocyte-Derived Dendritic Cells: Role of the cag Pathogenicity Island. Infect. Immun.
72: 4480-4485
[Abstract]
[Full Text]
-
Qadri, F, Bhuiyan, T R, Dutta, K K, Raqib, R, Alam, M S, Alam, N H, Svennerholm, A-M, Mathan, M M
(2004). Acute dehydrating disease caused by Vibrio cholerae serogroups O1 and O139 induce increases in innate cells and inflammatory mediators at the mucosal surface of the gut. Gut
53: 62-69
[Abstract]
[Full Text]
-
Yamasaki, R., Yokota, K., Okada, H., Hayashi, S., Mizuno, M., Yoshino, T., Hirai, Y., Saitou, D., Akagi, T., Oguma, K.
(2004). Immune response in Helicobacter pylori-induced low-grade gastric-mucosa-associated lymphoid tissue (MALT) lymphoma. J Med Microbiol
53: 21-29
[Abstract]
[Full Text]
-
Aras, R. A., Fischer, W., Perez-Perez, G. I., Crosatti, M., Ando, T., Haas, R., Blaser, M. J.
(2003). Plasticity of Repetitive DNA Sequences within a Bacterial (Type IV) Secretion System Component. JEM
198: 1349-1360
[Abstract]
[Full Text]
-
Orsini, B., Ottanelli, B., Amedei, A., Surrenti, E., Capanni, M., Del Prete, G., Amorosi, A., Milani, S., D'Elios, M. M., Surrenti, C.
(2003). Helicobacter pylori cag Pathogenicity Island Is Associated with Reduced Expression of Interleukin-4 (IL-4) mRNA and Modulation of the IL-4{delta}2 mRNA Isoform in Human Gastric Mucosa. Infect. Immun.
71: 6664-6667
[Abstract]
[Full Text]
-
Ohana, M, Okazaki, K, Oshima, C, Kawasaki, K, Fukui, T, Tamaki, H, Matsuura, M, Asada, M, Nishi, T, Uchida, K, Uose, S, Nakase, H, Iwano, M, Matsushima, Y, Hiai, H, Chiba, T
(2003). Inhibitory effects of Helicobacter pylori infection on murine autoimmune gastritis. Gut
52: 1102-1110
[Abstract]
[Full Text]
-
Garhart, C. A., Nedrud, J. G., Heinzel, F. P., Sigmund, N. E., Czinn, S. J.
(2003). Vaccine-Induced Protection against Helicobacter pylori in Mice Lacking Both Antibodies and Interleukin-4. Infect. Immun.
71: 3628-3633
[Abstract]
[Full Text]
-
Straubinger, R. K., Greiter, A., McDonough, S. P., Gerold, A., Scanziani, E., Soldati, S., Dailidiene, D., Dailide, G., Berg, D. E., Simpson, K. W.
(2003). Quantitative Evaluation of Inflammatory and Immune Responses in the Early Stages of Chronic Helicobacter pylori Infection. Infect. Immun.
71: 2693-2703
[Abstract]
[Full Text]
-
Lundgren, A., Suri-Payer, E., Enarsson, K., Svennerholm, A.-M., Lundin, B. S.
(2003). Helicobacterpylori-Specific CD4+ CD25high Regulatory T Cells Suppress Memory T-Cell Responses to H. pylori in Infected Individuals. Infect. Immun.
71: 1755-1762
[Abstract]
[Full Text]
-
Garhart, C. A., Heinzel, F. P., Czinn, S. J., Nedrud, J. G.
(2003). Vaccine-Induced Reduction of Helicobacter pylori Colonization in Mice Is Interleukin-12 Dependent but Gamma Interferon and Inducible Nitric Oxide Synthase Independent. Infect. Immun.
71: 910-921
[Abstract]
[Full Text]
-
Stromberg, E., Edebo, A., Svennerholm, A.-M., Lindholm, C.
(2003). Decreased Epithelial Cytokine Responses in the Duodenal Mucosa of Helicobacter pylori-Infected Duodenal Ulcer Patients. CVI
10: 116-124
[Abstract]
[Full Text]
-
Akhiani, A. A., Pappo, J., Kabok, Z., Schon, K., Gao, W., Franzen, L. E., Lycke, N.
(2002). Protection Against Helicobacter pylori Infection Following Immunization Is IL-12-Dependent and Mediated by Th1 Cells. J. Immunol.
169: 6977-6984
[Abstract]
[Full Text]
-
Raghavan, S., Hjulstrom, M., Holmgren, J., Svennerholm, A.-M.
(2002). Protection against Experimental Helicobacter pylori Infection after Immunization with Inactivated H. pylori Whole-Cell Vaccines. Infect. Immun.
70: 6383-6388
[Abstract]
[Full Text]
-
Lehmann, F. S., Terracciano, L., Carena, I., Baeriswyl, C., Drewe, J., Tornillo, L., De Libero, G., Beglinger, C.
(2002). In situ correlation of cytokine secretion and apoptosis in Helicobacter pylori-associated gastritis. Am. J. Physiol. Gastrointest. Liver Physiol.
283: G481-G488
[Abstract]
[Full Text]
-
Thalmaier, U., Lehn, N., Pfeffer, K., Stolte, M., Vieth, M., Schneider-Brachert, W.
(2002). Role of Tumor Necrosis Factor Alpha in Helicobacter pylori Gastritis in Tumor Necrosis Factor Receptor 1-Deficient Mice. Infect. Immun.
70: 3149-3155
[Abstract]
[Full Text]
-
Tsutsumi, S., Tomisato, W., Hoshino, T., Tsuchiya, T., Mizushima, T.
(2002). Transforming Growth Factor-{beta}1 Is Responsible for Maturation-Dependent Spontaneous Apoptosis of Cultured Gastric Pit Cells. Exp. Biol. Med.
227: 402-411
[Abstract]
[Full Text]
-
Selbach, M., Moese, S., Meyer, T. F., Backert, S.
(2002). Functional Analysis of the Helicobacter pylori cag Pathogenicity Island Reveals Both VirD4-CagA-Dependent and VirD4-CagA-Independent Mechanisms. Infect. Immun.
70: 665-671
[Abstract]
[Full Text]
-
Hamanaka, Y, Nakashima, M, Wada, A, Ito, M, Kurazono, H, Hojo, H, Nakahara, Y, Kohno, S, Hirayama, T, Sekine, I
(2001). Expression of human {beta}-defensin 2 (hBD-2) in Helicobacter pylori induced gastritis: antibacterial effect of hBD-2 against Helicobacter pylori. Gut
49: 481-487
[Abstract]
[Full Text]
-
Quiding-Jarbrink, M, Lonroth, H, Ahlstedt, I, Holmgren, J, Svennerholm, A-M
(2001). Human gastric B cell responses can be induced by intestinal immunisation. Gut
49: 512-518
[Abstract]
[Full Text]
-
Segal, I., Ally, R., Mitchell, H.
(2001). Helicobacter pylori--an African perspective. QJM
94: 561-565
[Abstract]
[Full Text]
-
Wang, J., Brooks, E. G., Bamford, K. B., Denning, T. L., Pappo, J., Ernst, P. B.
(2001). Negative Selection of T Cells by Helicobacter pylori as a Model for Bacterial Strain Selection by Immune Evasion. J. Immunol.
167: 926-934
[Abstract]
[Full Text]
-
Eaton, K. A., Mefford, M., Thevenot, T.
(2001). The Role of T Cell Subsets and Cytokines in the Pathogenesis of Helicobacter pylori Gastritis in Mice. J. Immunol.
166: 7456-7461
[Abstract]
[Full Text]
-
Eaton, K. A., Mefford, M. E.
(2001). Cure of Helicobacter pylori Infection and Resolution of Gastritis by Adoptive Transfer of Splenocytes in Mice. Infect. Immun.
69: 1025-1031
[Abstract]
[Full Text]
-
O'Neil, D. A., Cole, S. P., Martin-Porter, E., Housley, M. P., Liu, L., Ganz, T., Kagnoff, M. F.
(2000). Regulation of Human beta -Defensins by Gastric Epithelial Cells in Response to Infection with Helicobacter pylori or Stimulation with Interleukin-1. Infect. Immun.
68: 5412-5415
[Abstract]
[Full Text]
-
Rossi, G., Fortuna, D., Pancotto, L., Renzoni, G., Taccini, E., Ghiara, P., Rappuoli, R., Del Giudice, G.
(2000). Immunohistochemical Study of Lymphocyte Populations Infiltrating the Gastric Mucosa of Beagle Dogs Experimentally Infected with Helicobacter pylori. Infect. Immun.
68: 4769-4772
[Abstract]
[Full Text]
-
Wang, J., Fan, X., Lindholm, C., Bennett, M., O'Connoll, J., Shanahan, F., Brooks, E. G., Reyes, V. E., Ernst, P. B.
(2000). Helicobacter pylori Modulates Lymphoepithelial Cell Interactions Leading to Epithelial Cell Damage through Fas/Fas Ligand Interactions. Infect. Immun.
68: 4303-4311
[Abstract]
[Full Text]
-
Tanahashi, T., Kita, M., Kodama, T., Yamaoka, Y., Sawai, N., Ohno, T., Mitsufuji, S., Wei, Y.-P., Kashima, K., Imanishi, J.
(2000). Cytokine Expression and Production by Purified Helicobacter pylori Urease in Human Gastric Epithelial Cells. Infect. Immun.
68: 664-671
[Abstract]
[Full Text]
-
Simpson, K. W., Strauss-Ayali, D., Scanziani, E., Straubinger, R. K., McDonough, P. L., Straubinger, A. F., Chang, Y.-F., Domeneghini, C., Arebi, N., Calam, J.
(2000). Helicobacter felis Infection Is Associated with Lymphoid Follicular Hyperplasia and Mild Gastritis but Normal Gastric Secretory Function in Cats. Infect. Immun.
68: 779-790
[Abstract]
[Full Text]
-
MASTROENI, P, BOWE, F, CAHILL, R, SIMMONS, C, DOUGAN, G
(1999). Vaccines against gut pathogens. Gut
45: 633-635
[Full Text]
-
Ahlstedt, I., Lindholm, C., Lonroth, H., Hamlet, A., Svennerholm, A.-M., Quiding-Jarbrink, M.
(1999). Role of Local Cytokines in Increased Gastric Expression of the Secretory Component in Helicobacter pylori Infection. Infect. Immun.
67: 4921-4925
[Abstract]
[Full Text]
-
ZEVERING, Y, JACOB, L, MEYER, T F
(1999). Naturally acquired human immune responses against Helicobacter pylori and implications for vaccine development. Gut
45: 465-474
[Full Text]