2003, Number 2
<< Back Next >>
Ann Hepatol 2003; 2 (2)
Serum interleukin 6 and interleukin 12 levels in children with chronic hepatitis HBV treated with interferon alpha
Góra-Gbka M, Liberek A, Szydowska-ysiak W, Bako W, Korzon M
Language: English
References: 54
Page: 92-97
PDF size: 66.05 Kb.
Text Extraction
Introduction: The course of HBV infection and the outcome of interferon alpha (IFNα) therapy of patients with chronic hepatitis B, is determined by the antiviral immune response of the host. The aim of the study was to investigate 1) the correlation between IL-6 and IL-12 serum levels and biochemical and histopathological changes in children with chronic hepatitis B, 2) predictive value of pre-treatment serum levels of these cytokines in patients treated with interferon alpha and 3) changes in serum levels of these cytokines after interferon alpha treatment.
Methods: Serum levels of IL-6, IL-12 (heterodimer p70) and IL-12 (heterodimer p70 & p40 subunit) were determined by specific ELISA in 39 children with chronic hepatitis B on the first and the last day of IFNα therapy.
Results: Serum levels of IL-6, IL-12 (p70) and IL-12 (p70&p40) were respectively within the following ranges of values: 0-1.7 pg/mL, 3.0-85.1pg/mL, 93.7-442.7 pg/mL and they showed no correlation with biochemical and histopathological changes. The pre-treatment cytokines levels in patients who responded and those who did not respond to IFNa therapy did not differ statistically. There was no statistical difference between the end and pre-treatment cytokines levels in both groups.
Conclusions: Serum levels of IL-6 and IL-12 do not reflect the inflammatory activity of hepatitis and have no predictive value of positive response to the IFNα therapy in children with chronic hepatitis B. Serum IL-6 and IL-12 levels at the end of INFα treatment do not inform of their role in immunological changes which take place while inhibition of HBV replication or virus clearance.
REFERENCES
Andus T, Bauer J, Gerok W. Effects of cytokines on the liver. Hepatology 1991; 13: 364-375.
Byl B, Roucloux I, Crusiaux A, Dupont E, Deviere J. Tumor Necrosis Factor a and Interleukin 6 plasma Levels in Infected Cirrhotic Patients. Gastroenterol 1993; 104: 1492-1497.
Czerwionka-Szaflarska M, Pawlowska M, Halota W. Interleukin (Il-1 beta, Il-2, Il-4 and Il-6) concentrations in patients with chronic B and C hepatitis. Materialy Naukowe Konferencji Polskiego Towarzystwa Hepatologicznego maj 1996; 67.
Gregorio GV, Hussain M, Mieli-Vergani G, Vergani D. Elevated Il-6 levels presage and accompany anti-HBe seroconversion during interferon treatment of chronic hepatitis B virus infection. J Hepatol 1996; 26 (suppl): 83.
Kakumu S, Shinagawa T, Ishikawa T, Yoshioka K, Wakita T, Ito Y, Takayanagi M, Ida N. Serum interleukin 6 levels in patients with chronic hepatitis B. Am J Gastroenterol 1991: 86: 1804-1808.
Pawlowska M, Czerwionka-Szaflarska M, Halota W. Cytokin (Il-1 beta, Il-2, Il-4 and Il-6) concentration in patients with chronic hepatitis during the treatment with interferon-alpha. Materialy Naukowe Konferencji Polskiego Towarzystwa Hepatologicznego 30 maj 1996; 68.
Socha P, Janas R, Socha J, Pawlowska J, Wozniak M, Woynarowski M. Czy TNF-a i Il-6 moga byc pomocne w ocenie przewleklego zapalenia watroby u dzieci? Wiad Lek 1994; 47: 493-496.
Tilg H, Wilmer A, Vogel W, Herold M, Nölchen B, Judmaier G, Huber C. Serum levels of cytokines in chronic liver diseases. Gastroenterol 1992; 103:264-274.
Torre D, Zeroli C, Giola M, Ferrario G, Fiori GP, Bonetta G, Tambini R. Serum levels of interleukin-1 alpha, interleukin-beta, interleukin-6, and tumor necrosis factor in patients with acute viral hepatitis. Clin Infect Dis 1994; 18 (2): 194-198.
Kakumu S, Fukatsu A, Shinagawa T, Kurokawa S, Kusakabe A. Localization of intrahepatic interleukin 6 in patients with acute and chronic liver disease. J Clin Pathol 1992; 45: 408-411.
Ohno H, Kaneko S, Kobayashi K, Murakami S. Human Hepatitis B Virus Enhancer 1 is Responsive to Human Interleukin-6. J Med Virol 1997; 52: 413-418.
Schmitt E, Hoehn P, Huels C. T helper type 1 development of naive CD4+ t cells requires the coordinate action of interleukin 12 and interferon gamma and is inhibited by transforming growth factor-beta. Eur J Immunol 1994; 24: 793-798.
Vingerhoets J, Michielsen P, Vanham G, Bosmans E, Paulij W, RamonA, Palcmans P, et al. HBV-specific lymphoproliferative and cytokine responses in patients with chronic hepatitis B. J Hepatol 1998; 28: 8-16.
Lee Y, Park US, Choi I, Yoon SK, Park YM, Lee YI. Human Interleukin 6 Gene Is Activated by Hepatitis B Virus-X Protein in Human Hepatoma Cells. Clin Cancer Res 1998; 4: 1711-1717.
Müller C, Zielinski C. Interleukin 6 production by peripheral blood monocytes in patients with chronic liver disease and acute viral hepatitis. J Hepatol 1992; 15: 372-377.
Nobuo I, Shingou S, Touko H, Kazuo H, Tetsunosuke K, Yoshiharu M, Masayoshi K. An enzyme-linked immunosorbent assay for measurement of human interleukin-6. J Immunol Methods 1990; 133: 279-284.
Rossol S, Marinos G, Carruci P, Singer MV, Williams R, Naoumov N. Interleukin-12 Induction of Th1 Cytokines is Important for Viral Clearance in Chronic Hepatitis B. J Clin Invest 1997; 99: 3025-3033.
Gabriel A, Ziólkowski A. Zasady numerycznej oceny biopsji watroby. Propozycja protokolu badania histopatologicznego bioptatu wartroby w diagnostyce przewleklych zapalen. Hepatol Pol 1997; 4(suppl1): 33-39
Scheuer PJ, Davies SE, Dhillon AP. Histopathological aspects of viral hepatitis. J Viral Hepat 1996; 3: 277-283.
Kakumu S, Shinagawa T, Ishikawa T, Yoshioka K, Wakita T, Ida N. Interleukin 6 production by peripheral blood mononuclear cells in patients with chronic hepatitis B virus infection and primary biliary cirrhosis. Gastroenterol Jap 1993; 28: 18-24.
Cielecka B. Aktualne problemy rozpoznawania i leczenia chorób watroby wywolanych zakazeniem wirusem HBV u dzieci. Przegl Ped 1993; 23: 627-633.
Woynarowski M, Pawlowska J, Socha J. Przewlekle zapalenie watroby u dzieci. Medipress Pediatria 1995; 4: 8-13.
Woynarowski M. Specifity of viral liver disease in children. Hepatol Pol 1997; 4: 73-76.
Alexander G. Historia naturalna i leczenie wirusowego zapalenia watroby typu B. Zeszyty hepatologiczne 1992; 5: 15-19.
Bortolotti F, Cadrobbi P, Crivellaro C, Guido M, Rugge M, Noventa F, Calzia R, et al. G. Long-term outcome of chronic type B hepatitis in patients who acquire hepatitis B virus infection in childhood. Gastroenterology 1990; 99: 805-810.
Bruguera M, Amat L, Garcia O, Lambruschini N, Carnicer J, Bergada A, Martin-Orte E, et al. Treatment of chronic hepatitis B in children with recombinant alfa interferon. Different response according to age at infection. J Clin Gastroenterol 1993; 17: 296-299.
Karasinska M. Aspekty epidemiologiczne i nastepstwa przewleklego zakazenia wirusem Hepatitis B (WHB) u dzieci. Wiad Lek 1991; 44: 26-29.
Sun Y, Tokushige K, Isono E, Yamauchi K, Obata H. Elevated serum Il-6 levels in patients with acute hepatitis. J Clin Immunol 1992; 12: 197-200.
Gately MK, Wolitzky AG, Quinn PM, Chizzonite R. Regulation of human cytolitic lymphocyte responces by interleukin 12. Cell 1992; 143: 127-142.
Kovacs EJ. Fibrogenic cytokines: the role of immune mediators in the development of scar tissue. Immunol Today 1991; 12: 17-23.
Lee WM. Hepatitis B Virus Infection. N Engl J Med 1997; 337: 1743-1745.
Louis-Jacques O, Olson AD. Cost-Benefit Analysis of Interferon Therapy in Children with Chronic Active Hepatitis B. J Pediatr Gastroenterol Nutr 1997; 24: 25-32.
Lau JYN, Wright TL. Molecular virology and pathogenesis of hepatitis B. Lancet 1993; 342: 1335-1340.
Mondelli MU. Role of the immune system in liver damage. Hepatol Pol 1997; 4: 89-90.
Guida S, Fiore M, Scotese I, Iorio R, Gaentaniello L, Vegnente A, Pignata C. Defective interleuki-2 production in children with chronic hepatitis B: role of adherent cells. J Pediatr Gastroenterol Nutr 1997; 24: 312-316.
Waage A, Kaufman C, Espevik T. Interleukin 6 in synovial fluid from patients with arthritis. Clin Immunol Immunopathol 1989; 5: 394-400.
Gerok W, Decker K, Andus T, Gross V. Cytokines and the Liver. Falk Symposium 78. Kluwer Academic Publishers 1995; 14-31, 58-83.
Al.-Wabel A, Al.-Janadi M, Raziuddin S. Cytokine profile of viral and autoimmune chronic active hepatitis. J Allergy Clin Immunol 1993; 92: 902-908.
Gladysz A, Simon K, Woynarowski M. Wyniki leczenia interferonami przewleklych wirusowych zapalen watroby u doroslych i dzieci–badanie ogólnopolskie. Hepatol Pol 1997; 4 (supll. 1): 48-52.
Torre D, Tambini R. Interferon-a therapy for chronic hepatitis B in children: a meta-analysis. Clin Infect Dis 1996; 23: 131-137.
Chisari FV, Ferrari C. Hepatitis B virus immunopathogenesis. Annu Rev Immunol 1995; 13: 29-60.
Jonas MM. Interferon–a for viral hepatitis. J Pediatr Gastroenterol Nutr 1996; 23: 93-106.
Juszczyk J. Mechanizmy smierci komórki watrobowej. Zeszyty hepatologiczne1998; 9: 19-24.
Mantovani A. The Interplay between Primary and Secondary Cytokines. Cytokines Involved in the Regulation of Monocyte Recruitment. Drugs 1997; 54 (suppl): 15-23.
Bertagnolli MM, Lin BY, Young D, Herrmann SH. Il-12 augments antigen-dependent proliferation of activated T lymphocytes. J Immunol 1992; 149: 3778-3783.
D‘Andrea A, Rengaraju M, Valiante NM, Chehimi J, Kubin M, Aste M, Chan SH, et al. Production of natural killer cell stimulatory factor (Interleukin-12) by peripheral blood mononuclear cells. J Exp Med 1992; 176: 1387-1393.
Kiniva M, Gately M, Gubler U, Chizzonite R, Fargeas C, Delespesse G. Recombinant interleukin-12 suppresses the synthesis of immunoglobulin E by interleukin–4 stimulated lymphocytes. J Clin Invest 1992: 262-266.
Kobayashi M, Fitz L, Ryan M. Identification and purification of Natular Killer cell stimulatory factor (NKSF), a cytokine with multiple biologic effects on human lymphocytes. J Exp Med 1989; 170: 827-846.
Kubin M. Interleukina-12–nowa cytokina o potencjalnym znaczeniu klinicznym. Klinika 1995; 3: 14-17.
Manetti R, Parronchi P, Giudizi MG. Natural killer cell stimulatory factor interleukin 12 (Il-12) induces T helper type 1 (Th1) – specific immune responses and inhibits the development of Il-4 producing Th cells. J Exp Med 1993; 177: 1199-2004.
Trinchieri G. Interleukin 12: a proinflamatory cytokine with immunoregulatory functions that bridge innate resistance and antigen specific adaptive immunity. Annu Rev Immunol 1995; 1995: 13: 251-276.
Wenner CA, Guler ML, Macatonia SE, O‘Garra A, Murphy KM. Roles if INF-gamma and INF-alpha in Il-12-induced T helper cell-1 development. J Immunol 1996; 156: 1442-1447.
Schlaak JF, Tully G, Löhr HF, Gerken G, Meyer zum Büschenfelde. HBV-specific immune defect in chronic hepatitis B (CHB) is correlated with a dysregulation of pr- and anti-inflammatory cytokines. Clin Exp Immunol 1999; 115: 508-514.
Wolf SF, Sieburth D, Sypek J. Interleukin-12: a key modulator of immune function. Stem Cells 1994; 12: 154-168.