Journal of the Chinese Medical Association
Volume 73, Issue 2 , Pages 67-71, February 2010

Serum Interleukin-12 Levels in Alcoholic Liver Disease

Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital, and National Yang-Ming University School of Medicine, Taipei, Taiwan, R.O.C.

Received 19 June 2009; accepted 15 December 2009.

Article Outline

Background

Interleukin (IL)-12 is a proinflammatory cytokine produced by antigen-presenting cells upon stimulation by diverse stimuli. This study aimed to explore the relationship between IL-12 serum levels and different stages of alcoholic liver disease, alcoholic intake status and abstinence from alcohol.

Methods

A total of 35 healthy controls without alcohol consumption and 94 patients with alcoholic liver disease (17 with alcoholic steatosis, 37 with alcoholic hepatitis, 40 with alcoholic cirrhosis) were included. Their serum IL-12 levels were measured and followed-up at the 3rd, 6th and 9th months. Data were further analyzed according to abstinence from alcohol or not.

Results

Mean serum IL-12 levels were higher in the alcoholic hepatitis group (163.1 ± 57.8 pg/mL) than in the alcoholic liver cirrhosis group (110.5 ± 41.6 pg/mL) and alcoholic steatosis group (74.4 ± 26.2 pg/mL). All of these 3 alcoholic groups had higher serum IL-12 levels than the control group (39.3 ± 8.3 pg/mL; p < 0.02). Among the patients who abstained from alcohol, there was no difference in serum IL-12 levels between control and steatosis patients at the 9th month, but the serum IL-12 levels of the hepatitis and cirrhosis groups were still higher than in the control group (p < 0.001 and p = 0.001, respectively). In addition, the patients who continued to drink alcohol had higher serum IL-12 levels than those who abstained from alcohol in the steatosis, hepatitis and cirrhosis groups. At the cut-off value of 54 pg/mL, IL-12 had good sensitivity and specificity in the diagnosis of alcoholic liver disease.

Conclusion

Serum IL-12 levels reflected the different stages of alcoholic liver disease and can represent the status of continuous alcohol consumption. It has the potential to be a biomarker of alcoholic liver disease.

Key Words:  alcoholic cirrhosis , alcoholic hepatitis , alcoholic liver disease , cytokine , interleukin 12

No full text is available. To read the body of this article, please view the PDF online.

 

Back to Article Outline

References 

  1. Tilg H , Diehl AM . Cytokines in alcoholic and nonalcoholic steatohepatitis . N Engl J Med . 2000;343:1467–1476
  2. McClain CJ , Hill DB , Schmidt J , Diehl AM . Cytokines and alcoholic liver disease . Semin Liver Dis . 1993;13:170–182
  3. Huang YS , Chan CY , Wu JC , Pai CH , Chao Y , Lee SD . Serum levels of interleukin-8 in alcoholic liver disease: relationship with disease stage, biochemical parameters and survival . J Hepatol . 1996;24:377–384
  4. Hendrzak JA , Brunda MJ . Interleukin-12: biologic activity, therapeutic utility, and role in disease . Lab Invest . 1995;72:619–637
  5. Manetti R , Parronchi P , Giudizi MG , Piccini MP , Maggi E , Trinchieri G . 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;177:1199–1204
  6. Laso FJ , Iglesias MC , Lopez CA , Ciudad J , San Miguel JF , Orfao A . Increased interleukin-12 serum levels in chronic alcoholism . J Hepatol . 1998;28:771–777
  7. Jaana L , Johanna H , Heidi K , Kimmo J , Petra A , Onni N . Immune responses to ethanol metabolites and cytokine profile differentiate alcoholics with or without liver disease . Am J Gastroenterol . 2005;100:1303–1310
  8. Heinzel FP , Rerko RM , Ling P , Hakimi J , Schoenhaut DS . Interleukin-12 is produced in vivo during endotoxemia and stimulates synthesis of gamma interferon . Infect Immun . 1994;62:4244–4249
  9. Chan SH , Perussia B , Gupta JW , Kobayashi M , Pospisil M , Young HA . Induction of IFN-γ production by NK cell stimulatory factor (NKSF): characterization of the responder cells and synergy with other inducers . J Exp Med . 1991;173:869–879
  10. D'Andrea A , Ma X , Aste-Amezaga M , Paganin C , Trinchieri G . Stimulatory and inhibitory effects of IL-4 and IL-13 on production of cytokines by human peripheral blood mononu-clear cells: priming for IL-12 and TNF-alpha production . J Exp Med . 1995;181:537–546
  11. Koen V , Iraide A , Massimo G , Patrick M . Inhibiting cytokines of the interleukin-12 family: recent advances and novel challenge . J Pharm Pharmacol . 2004;6:145–160
  12. Tilg H , Kaser A , Moschen AR . How to modulate inflammatory cytokines in liver disease . Liver Int . 2006;26:1029–1039
  13. Bok YK , Eugene K , Tae SK . Regulatory mechanisms and their therapeutic implications of interleukin-12 production in immune cells . Cell Signal . 2005;17:665–673
  14. Moller DR , Wysocka M , Greenlee BM , Ma X , Wahl L , Trinchieri G . Inhibition of human interleukin-12 production by pentoxifylline . Immunology . 1997;91:197–203
  15. Akriviadis E , Botla R , Briggs W , Han S , Reynolds T , Shakil O . Pentoxifylline improves short-term survival in severe acute alcoholic hepatitis: a double-blind, placebo-controlled trial . Gastroenterology . 2000;119:1637–1648

PII: S1726-4901(10)70004-6

doi:10.1016/S1726-4901(10)70004-6

Journal of the Chinese Medical Association
Volume 73, Issue 2 , Pages 67-71, February 2010

Article Tools