Articles
 

IL-10, TNF-α and IFN-γ Levels in Serum and Stomach Mucosa of Helicobacter Pylori-Infected Patients

Abstract

H. pylori  is a human pathogen that colonizes the epithelium of the stomach. The host immune response may influence the disease process, where cytokines play important roles in the development of disease. In this study, the concentrations of selected cytokines in the gastric antrum and stomach body mucosa and also in the serum were evaluated.
Eighty patients according to their rapid urease test were divided into two groups: H. pylori positive (n=39) and H. pylori-negative (n=41). The concentrations of cytokines in biopsies and serum were determined by ELISA method. The mean TNF-α and IFN-γ levels in the infected group were significantly higher than that of uninfected patients. In contrast, IL-10 level in most patients was undetectable. The mean antral of stomach TNF-α  and IFN-γ levels were significantly higher than that of the stomach body.
IFN-γ  serum level showed positive correlation with antrum and stomach body levels, whereas no correlation was found in TNF-α in different samples.
Higher levels of TNF-α and IFN-γ in antral indicate that the colonization of bacteria in the antrum may be higher than stomach body (culture results from two sites support this statement). Increased serum level of IFN-γ  indicates the activation of circulating-T cells against infection. Induced H. pylori-related TNF-α is concentrated is gastric mucosa and this pathogen does not cause any significant change in the serum level of this cytokine. Therefore H.  pylori  by inducing certain inflammatory cytokines but  not  IL-10 may contribute  the process of disease development.

1. Matysiak-Budnik T, Megraud F. Helicobacter pylori infec- tion and gastric cancer. Eur J Cancer 2006; 42(6):708-16.
2. Krejs GJ. Gastric Cancer: Epidemiology and Risk Factors.Dig Dis 2010; 28(4-5):600-3.
3. Maciorkowska E, Panasiuk A, Kaczmarski M. Concentration of gastric mucosal cytokines in children with food allergy and Helicobacter pylori infection. World J Gastroenterol 2005; 11(43):6751-6.
4. Bergman M, Prete GD, Kooyh YV, Appelmelk B.Helicobacter pylori phase variation, immune modulation and gastric autoimmunity. Nat Rev Microbiol 2006; 4(2):151-9.
5. Asadullah, K, Sterry W, Volk HD. Interleukin-10 therapy- review of a new approach. Pharmacol Rev 2003; 55(2):241-69.
6. Bazzoni F, Beutler B. The tumor necrosis factor ligand and receptor families. N Engl J Med 1996; 334(26):1717-25.
7. Jonasch, E, Haluska FG. Interferon in oncological practice:review of interferon biology, clinical applications, and toxicities. Oncologist 2001; 6(1):34-55.
8. Borriello SP, Murray P, Funke G. Topley & Wilsons’ Microbiology & Microbial Infections: Vol.2. London Hodder Arnold, 2005.
9. Silva JS, Morrissey PJ, Grabstein KH, Mohler KM, Anderson D, Reed SG. Interleukin 10 and interferon gamma regulation of experimental Trypanosoma cruzi infection. J Exp Med 1992; 175(1):169-74.
10. Komatsu M, Kobayashi D, saito K, Furuya D, Yagihashi A, Araake H, et al. Tumor necrosis factor-alpha in serum of patients with inflammatory bowel disease as measured by a highly sensitive immuno-PCR. Clin Chem 2001;47(7):1297–301.
11. Inada M, Miyaura C. Cytokines in bone diseases. Cytokine and postmenopausal osteoporosis. Clin Calcium 2010;20(10):1467-72.
12. Kuzuhara T, Suganuma M, Oka K, Fujiki H. DNA-binding activity of TNF-α inducing protein from Helicobacter pylori. Biochem Biophys Res Commun 2007; 362(4):805–10.
13. Guiraldes E, Duarte I, Pena A, Godoy A, Espinosa MN, Bravo R, et al. Proinflammatory cytokine expression in gastric tissue from children with Helicobacter pylori- associated gastritis. J Pediatr Gastroenterol Nutr 2001;33(2):127-32.
14. Sun J, Aoki K, Zheng JX, Su BZ, Ouyang XH, Misumi J.Effect of NaCl and Helicobacter pylori vacuolating cytotoxin on cytokine expression and viability. World J Gastroenterol 2006; 12(14):2174-80.
15. Senthilkumar C, Niranjali S, Jayanthi V, Ramesh T, Devaraj H. Molecular and histological evaluation of tumor necrosis factor-alpha expression in Helicobacter pylori-mediated gastric carcinogenesis. J Cancer Res Clin Oncol 2011;137(4):577-83.
16. Aderka D, Engelmann H, Maor Y, Brakebusch C, Wallach D. Stabilization of the bioactivity of tumor necrosis factor by its soluble receptors. J Exp Med 1992; 175(2):323–9.
17. Fujita M, Ikegame S, Harada E, Ouchi H, Inoshima I, Watanabe K, et al . TNF receptor 1 and 2 contribute in different ways to resistance to Legionella pneumophila- induced mortality in mice. Cytokine 2008; 44(2):298–303.
18. Bayraktaroglu, T, Aras AS, Aydemir S, Davutoglu C, Ustundag Y, Atmaca H, et al. Serum levels of tumor necrosis factor-alpha, interleukin-6 and interleukin-8 are not increased in dyspeptic patients with Helicobacter pylori-associated gastritis. Mediators Inflamm 2004; 13(1):25-8.
19. Fan XG, Chua A, Fan XJ, Keeling PW. Increased gastric production of interleukin-8 and tumour necrosis factor in patients with Helicobacter pylori infection. J Clin Pathol 1995; 48(2):133-6.
20. Klausz G, Tiszai A, Lenart Z, Gyulai Z, Tiszlavicz L, Hogye M, et al. Helicobacter pylori-induced immunological responses in patients with duodenal ulcer and in patients with cardiomyopathies. Acta Microbiol Immunol Hung 2004;51(3):311-20.
21. Lopes AI, Quiding-Jarbrink M, Palha A, Ruivo J, Monteiro L, Oleastro M, et al. Cytokine expression in pediatric Helicobacter pylori infection. Clin Diagn Lab Immunol 2005; 12(8):994-1002.
22. Romero-Adrián TB, Leal-Montiel J, Monsalve-Castillo F, Mengual-Moreno E, McGregor EG, Perini L, et al. Bacterial factors and the role of cytokines in the immune response. Curr Microbiol 2010; 60(2):143-55.
23. Zavros Y, Merchant JL. Modulating the cytokine response to treat Helicobacter gastritis. Biochem Pharmacol 2005;69(3):365-71.
24. Perfetto B, Buommino E, Canozo N, Paoletti I, Corrado R, Greco R, et al. Interferon-gamma cooperates with Helicobacter pylori to induce iNOS-related apoptosis in AGS gastric adenocarcinoma cells. Res Microbiol 2004;155(4):259-66.
25. Sawai N, Kita M, Kodama T, Tanahashi T, Yamaoka Y, Tagawa Y, et al. Role of Gamma Interferon in Helicobacter pylori-Induced Gastric Inflammatory Responses in a Mouse Model. Infect Immun 1999; 67(1):279–85
26. Quiding-Jarbrink M, Lundin BS, Lonroth H, Svennerholm AM. CD4+ and CD8+ T cell responses in Helicobacter pylori infected individuals. Clin Exp Immunol 2001;123(1):81-7.
27. Lee JY, Kim HY, Kim KH, Kim SM, Jang MK, Park JY, et al. Association of polymorphism of IL-10 and TNF-α genes with gastric cancer in Korea. Cancer Lett 2005; 225(2):207-14.
28. Algood HM, Cover TL. Helicobacter pylori Persistence: Overview of Interactions between H.pylori and Host Immune Defenses. Clin Microbiol Rev 2006; 19(4):596-613.
29. Guiney DG, Hasegawa P, Hasegawa P, Cole SP.Helicobacter pylori preferentially induces interleukin 12 (IL-12) rather than IL-6 or IL-10 in human dendritic cells. Infect Immun 2003; 71(7):4163-6.
30. Szkaradkiewicz A, Karpinski TM, Drews M, Borejsza-Wysocki M, Majewski P, Andrzejewska E. Natural killer cell cytotoxicity and immunosuppressive cytokines (IL-10, TGF-beta1) in patients with gastric cancer. J Biomed Biotechnol 2010;1-7.

Files
IssueVol 10, No 4 (2011) QRcode
SectionArticles
Keywords
Helicobacter pylori infection IFN-γ IL-10 TNF-α

Rights and permissions
Creative Commons License This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
How to Cite
1.
Abdollahi H, Shams S, Zahedi MJ, Darvish Moghadam S, Hayatbakhsh MM, Jafarzadeh A. IL-10, TNF-α and IFN-γ Levels in Serum and Stomach Mucosa of Helicobacter Pylori-Infected Patients. Iran J Allergy Asthma Immunol. 1;10(4):267-271.