CYTOKINE PROFILE IN PATIENTS WITH CHRONIC VIRUS HEPATITIS COMPLICATED WITH FIBROSIS AND CIRRHOSIS
https://doi.org/10.15789/1563-0625-2006-4-539-546
Abstract
Abstract. In present study, a comparative analysis of spontaneous and LPS-stimulated production of Th1/ Th2 (IFN-γ/IL-4, IL-13), and monocyte-derived pro- and anti-inflammatory cytokines (TNF-α/IL-10) was carried out in blood cell cultures of healthy donors and the patients with chronic viral hepatitis complicated with liver fibrosis and cirrhosis. The patients’ cells exhibited an increased production of both Th1/proinflammatory and Th2/anti-inflammatory cytokines. Meanwhile, hepatitis-induced cirrhotic transformation correlates with enhancement of spontaneous IL-4 and IL-13 production (not observed in fibrosis patients), and progressive increase of spontaneous IFN-γ, TNF-α and IL-10 secretion. In turn, the progression of cirrhosis is connected with increase of pro-inflammatory blood activity and reduction of anti-inflammatory potential. E.g., the patients with grade C cirrhosis have significantly higher index of TNF-α/IL-10 and IFN-γ/IL-10 ratio, as compared to the grade A patients. Moreover, we revealed a positive correlation of TNF-α/IL-10 ratio with cytolysis and severity of cirrhosis (Child-Pugh score), and a reverse correlation between the grade of liver cirrhosis and LPS-induced stimulation index of IL-10. Predominance of pro-inflammatory cytokines, displayed as increased IFN-γ/IL-10 ratio, was also associated with presence of anemia. Hence, the profile of cytokines produced by peripheral blood cells reflects some clinical features in the patients with chronic virus hepatitis complicated with fibrosis and cirrhosis.
About the Authors
E. R. ChernykhRussian Federation
N. M. Starostina
Russian Federation
O. Yu. Leplina
Russian Federation
E. Ya. Shevela
Russian Federation
S. V. Agapitova
Russian Federation
M. V. Shipunov
Russian Federation
A. A. Ostanin
Russian Federation
V. A. Kozlov
Russian Federation
References
1. Abayli B., Canataroglu A., Akkiz H. Serum profile of T helper 1 and T helper 2 cytokines in patients with chronic hepatitis C virus infection // Turk. J. Gastroenterol. - 2003. - Vol. 1. - P. 7-11.
2. Andrews N. C. Anemia of inflammation: the cytokine-hepcidin link // J. Clin. Invest. - 2004. - Vol. 113. - P. 1251-1253.
3. Bataller R., Brenner D.A. Liver fibrosis // Clin. Invest. - 2005. - Vol. 115. - P. 209-218.
4. Bertoletti A., Maini M.K. Protection or damage: a dual role for the virus-specific cytotoxic T lymphocyte response in hepatitis B and C infection? // Curr. Opin. Immunol. -2000. - Vol. 12. - P. 403-408.
5. Chisari F.V., Ferrari C. Hepatitis B virus immunopathogenesis // Springer Semin Immunopathol.- 1995. - Vol. 13. - P. 29-60.
6. Cirera I., Bauer T.M., Navasa M. Bacterial translocation of enteric organisms in patients with cirrhosis // J. Hepatol. - 2001. - Vol. 34. - P. 32-37.
7. Iredale J.P. Cirrhosis: new research provides a basis for rational and targeted treatments // BMJ.- 2003.- Vol. 327.- P. 143-147.
8. Friedman S.L. Molecular regulation of hepatic fibrosis, an integrated cellular response to tissue injury // J. Biol. Chem. - 2000. - Vol. 275. - P. 2247-2250.
9. Gilles P.N., Fey G., Chisari F.V. Tumor necrosis factor alpha negatively regulates hepatitis B virus gene expression in transgenic mice // J. Virol. - 1992. - Vol. 66. - P. 3955-3960.
10. Iimuro Y., Gallucci R.M., Luster M.I., Kono H., Thurman R.G. Antibodies to tumor necrosis factor-alfa attenuate hepatic necrosis and inflammation caused by chronic exposure to ethanol in the rat // Hepatology. - 1997. - Vol. 26. - P. 1530-1537.
11. Kaviratne M., Hesse M., Leusink M., Cheever A.W., Davies S.J., McKerrow J.H., Wakefield L.M., Letterio J.J., Wynn T.A. IL-13 activates a mechanism of tissue fibrosis that is completely TGF-b independent. // J. Immunol. - 2004. - Vol. 173. - P. 4020-4029.
12. Kirschmann D.A., He X., Murasko D.M. Inhibition of macrophage-induced, antigen-specific T-cell proliferation by poly I: role of suppressor macrophages // Immunology. -1994. - Vol. 82. - P. 238-243.
13. Lalla C., Galli G., Aldrighetti L., Romeo R., MarianiM., Monno A., Nuti N., Colombo M., Callea F., Porcelli S.A., Panina-Bordignon P., Abrignani S., Casorati G., Dellabona P. Production of profibrotic cytokines by invariant NKT cells characterizes cirrhosis progression in chronic viral hepatitis // J. Immunol. - 2004. - Vol. 173. - P. 1417-1425.
14. Louis H., Van Laethem J.L., Wu W., Quertinmont E., Degraef C., Van den Berg K., Demols A., Goldman M., Le Moine O., Geerts A., Deviere J. Interleukin-10 controls neutrophilic infiltration, hepatocyte proliferation, and liver fibrosis induced by carbon tetrachloride in mice // Hepatology. - 1998. - Vol. 28. - P. 1607-1615.
15. Ludwiczek S., Aigner E., Theurl I., Weiss G. Cytokine-mediated regulation of iron transport in human monocytic cells // Blood. - 2003. - Vol.101. - P. 4148-4154.
16. Montaner L.J., da Silva R.P., Sun J., Sutterwala S., Hollinshead M., Vaux D., Gordon S. Type 1 and type 2 cytokine regulation of macrophages endocytosis: differential activation by IL-4/IL-13 as opposed to IFN-γ or IL-10 // J. Immunol. - 1999. - Vol. 162. - P. 4606-4613.
17. Napoli J., Bishop G.A., McGuinness P.H. Progressive liver injury in chronic hepatitis C infection correlates with increased intrahepatic expression of Th1-associated cytokines // Hepatology. - 1996. - Vol. 24.- P. 759-765.
18. Nelson D.R., Tu Z., Soldevila-Pico C., Abdelmalek M., Zhu H., Xu Y.L., Cabrera R., Liu C., Davis G.L. Long-term interleukin 10 therapy in chronic hepatitis C patients has a proviral and anti-inflammatory effect // Hepatology. - 2003. - Vol. 38. - P. 859-868.
19. Peters M. Actions of cytokines on the immune response and viral interactions: an overview // Hepatology. - 1996. - Vol. 23. - P. 909-916.
20. Raetsch C., Jia J.D., Boigk G., Bauer M., HahnE.G., Riecken E-O., Schuppan D. Pentoxifylline downregulates profibrogenic cytokines and procollagen I expression in rat secondary billiary fibrosis // Gut. - 2002. - Vol. 50. - P. 241-247.
21. Romagnani S., Parronchi P., D’Elios M.M., Romagnani P., Annunziato F., Piccinni M.P., Manetti R., Sampognaro S., Mavilia C, De Carli M., Maggi E., Del Prete G.F. An update on human Th1 and Th2 cells // Int. Arch. Allergy. Immunol. - 1997. - Vol. 113. - P. 153-156.
22. Sobue S., Nomura T., Ishikawa T., Ito S., Saso K., Ohara H., Joh T., Itoh M., Kakumu S. Th1/Th2 cytokine profiles and their relationship to clinical features in patients with chronic hepatitis C virus infection // J. Gastroenterol. - 2001. - Vol.36. - P. 544-551.
23. Sun Q.-L., Ran W. Review of cytokine profiles in patients with hepatitis // World J. Gastroenterol. - 2004. - Vol. 15. - P. 1709-1715.
24. Tilg H., Jalan R., Kaser A., Davies N.A., Offner F.A., Hodges S.J. Anti-tumor necrosis factor-alpha monoclonal antibody therapy in severe alcoholic hepatitis // J. Hepatol. - 2003. - Vol. 38. - P. 419-425.
25. Tilg H., Ulmer H., Kaser A., Weiss G. Role of IL-10 for induction of anemia during inflammation // J. Immunol. - 2002. - Vol. 169. - P. 2204-2209.
26. von Baehr V., Docke W.D., Plauth M., Liebenthal C., Kupferling S., Lochs H., Baumgarten R., Volk H.D. Mechanisms of endotoxin tolerance in patients with alcoholic liver cirrhosis: role of interleukin 10, interleukin 1 receptor antagonist, and soluble tumor necrosis factor receptors as well as effector cell desensitization // Gut. - 2000. - Vol. 47. - P. 281-287.
27. Weiss G., Goodnough L. T. Anemia of chronic disease // N. Engl. J. Med. - 2005. - Vol. 352. - P. 1011 - 1023.
28. Weiss G., Bogdan C., Hentze M.W. Pathways for the regulation of macrophage iron metabolism by the anti-inflammatory cytokines IL-4 and IL-13 // J. Immunol. - 1997. - Vol. 158. - P. 420-426.
29. Wel R., Chen B., Gan T.F., Zhou X.M., Zhang Y.Q., Ren D.L. Application of flow cytometry to analyzing the activation states of peripheral blood mononuclear cells CD14 macrophage // Chin. J. Lab. Med. - 2003. - Vol. 26. - P. 1-4.
Review
For citations:
Chernykh E.R., Starostina N.M., Leplina O.Yu., Shevela E.Ya., Agapitova S.V., Shipunov M.V., Ostanin A.A., Kozlov V.A. CYTOKINE PROFILE IN PATIENTS WITH CHRONIC VIRUS HEPATITIS COMPLICATED WITH FIBROSIS AND CIRRHOSIS. Medical Immunology (Russia). 2006;8(4):539-546. (In Russ.) https://doi.org/10.15789/1563-0625-2006-4-539-546