Abstract
The pathogenic role of immune‐mediated mechanisms in chronic hepatitis C virus (HCV) infection has not yet been elucidated. In this study, we report different cytokine expression profiles from hemodialysis (HD) and non‐HD HCV (+) patients. IL‐1β, IL‐2, IL‐4, IL‐6, TNF‐α, and TGF‐β1 serum levels, and liver biochemical parameters were determined in 85 individuals (41 HD patients and 44 non‐HD patients). Screening for HCV RNA and anti‐HCV antibodies was performed using qualitative and quantitative reverse transcription polymerase chain reaction (RT‐PCR), and standardized enzyme‐linked immunosorbent assay (ELISA) and recombinant immunoblot assay (RIBA) methods, respectively. IL‐4 and IL‐1β demonstrated decreased serum levels in non‐HD HCV carriers compared with healthy controls. Both T helper (Th) 1 and Th2 lymphocytes were highly associated with chronic HCV infection, as indicated by the increased IL‐2, IL‐4, and IL‐6 cytokine circulating levels in all chronic active hepatitis (CAH) patients examined. An enhanced Th2 response (IL‐4 and IL‐6) coupled with increased TNF‐α and IL‐1β serum levels was reported in HD HCV (–) patients. In conclusion, our data show that a virus‐induced Th2 and IL‐1β immunosuppression is an early event in HCV‐related chronicity. Long‐term HD specifically exerts a chronic effect on IL‐6, IL‐1β, and TNF‐α serum circulating levels. Irrespective of the HD status, HCV viremia, and liver biochemistry parameters, both Th1 and Th2 responses are highly associated with chronic HCV infection. J. Clin. Lab. Anal. 16:40–46, 2002. © 2002 Wiley‐Liss, Inc.
Keywords: hepatitis C virus, interleukin, serum, transforming growth factor‐β1, tumor necrosis factor‐α, viremia
REFERENCES
- 1. Choo QL, Kuo G, Weiner AJ, Overby LR, Bradley DW, Houghton M. 1989. Isolation of a cDNA clone derived from a blood‐borne non‐A, non‐B viral hepatitis genome. Science 244:359–362. [DOI] [PubMed] [Google Scholar]
- 2. Di Bisceglie AM. 1997. Hepatitis C and hepatocellular carcinoma. Hepatology 26(3 Suppl 1):34S–38S. [DOI] [PubMed] [Google Scholar]
- 3. Pereira BJ. 1999. Hepatitis C virus infection in dialysis: a continuing problem. Artif Organs 23:51–60. [DOI] [PubMed] [Google Scholar]
- 4. Ferrari C, Penna A, Bertoletti A, et al. 1998. Antiviral cell‐mediated immune responses during hepatitis B and hepatitis C virus infections. Recent Results Cancer Res 154:330–336. [DOI] [PubMed] [Google Scholar]
- 5. Mosmann TR, Cherwinski H, Bond MW, Giedlin MA, Coffman RL. I. Definition according to profiles of lymphokine activities and secreted proteins. J Immunol 136:2348–2357. [PubMed] [Google Scholar]
- 6. Mosmann TR, Sad S. 1996. The expanding universe of T‐cell subsets: Th1, Th2 and more. Immunol Today 17:138–146. [DOI] [PubMed] [Google Scholar]
- 7. Lucey DR, Clerici M, Shearer GM. 1996. Type 1 and type 2 cytokine dysregulation in human infectious, neoplastic, and inflammatory diseases. Clin Microbiol Rev 9:532–562. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 8. Eckels DD, Tabatabail N, Bian TH, et al. 1999. In vitro human Th‐cell responses to a recombinant hepatitis C virus antigen: failure in IL‐2 production despite proliferation. Hum Immunol 60:187–199. [DOI] [PubMed] [Google Scholar]
- 9. Varano B, Fantuzzi L, Puddu P, Borghi P, Belardelli F, Gessani S. 2000. Inhibition of the constitutive and induced IFN‐beta production by IL‐4 and IL‐10 in murine peritoneal macrophages. Virology 277:270–277. [DOI] [PubMed] [Google Scholar]
- 10. Desmet VJ, Gerber M, Hoofnagle JH, Manns M, Sheuer PJ. 1994. Classification of chronic hepatitis: diagnosis, grading and staging. Hepatology 19:1513–1519. [PubMed] [Google Scholar]
- 11. Garinis G, Spanakis N, Theodorou V, et al. 1999. Comparison of the enzyme‐linked immunosorbant assay III, recombinant immunoblot third generation assay, and polymerase chain reaction method in the detection of hepatitis C virus infection in haemodialysis patients. J Clin Lab Anal 13:122–125. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 12. Garinis G, Patrinos GP, Menounos P, et al. 2000. Evaluation of a minipool reverse transcription‐PCR screening method for the detection of hepatitis C virus infection in hemodialysis patients. Clin Chem 46:583–584. [PubMed] [Google Scholar]
- 13. Pearson FC, Dubczak J, Weary M, Anderson J. 1988. Determination of endotoxin levels and their impact on interleukin‐1 generation in continuous ambulatory peritoneal dialysis and hemodialysis. Blood Purif 6:207–212. [DOI] [PubMed] [Google Scholar]
- 14. Port FK, Vandekerkhove KM, Kunkel SL, Kluger MJ. 1987. The role of dialysate in the stimulation of interleukin‐1 production during clinical hemodialysis. Am J Kidney Dis 2:118–122. [DOI] [PubMed] [Google Scholar]
- 15. Haeffner‐Cavaillon N, Cavaillon JM, Ciancioni C, Bacle F, Delons S, Kazatchkine MD. 1989. In vivo induction of interleukin‐1 during hemodialysis. Kidney Int 35:1212–1218. [DOI] [PubMed] [Google Scholar]
- 16. Dinarello CA. 1997. Interleukin‐1. Cytokine Growth Factor Rev 8:253–265. [DOI] [PubMed] [Google Scholar]
- 17. Mege JL, Olmer M, Purgus R, et al. 1991. Haemodialysis membranes modulate chronically the production of TNF alpha, IL1 beta and IL6. Nephrol Dial Transplant 6:868–875. [DOI] [PubMed] [Google Scholar]
- 18. Cribier B, Schmitt C, Rey D, Lang JM, Kirn A, Stoll‐Keller F. 1998. Production of cytokines in patients infected by hepatitis C virus. J Med Virol 55:89–91. [DOI] [PubMed] [Google Scholar]
- 19. Alter HJ, Conry‐Cantilena C, Melpolder J, et al. 1997. Hepatitis C in asymptomatic blood donors. Hepatology 26(3 Suppl 1):29S–33S. [DOI] [PubMed] [Google Scholar]
- 20. Puoti C, Stati T, Magrini A. 1999. Serum HCV RNA titer does not predict the severity of liver damage in HCV carriers with normal aminotransferase levels. Liver 19:104–109. [DOI] [PubMed] [Google Scholar]