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World J Gastroenterol. Apr 28, 2006; 12(16): 2563-2568
Published online Apr 28, 2006. doi: 10.3748/wjg.v12.i16.2563
Interleukin-6 and its soluble receptor in patients with liver cirrhosis and hepatocellular carcinoma
Maurizio Soresi, Lydia Giannitrapani, Fabio D’Antona, Ada Maria Florena, Emanuele La Spada, Angela Terranova, Melchiorre Cervello, Natale D’Alessandro, Giuseppe Montalto
Maurizio Soresi, Lydia Giannitrapani, Fabio D’Antona, Emanuele La Spada, Angela Terranova, Giuseppe Montalto, Dipartimento di Medicina Clinica e delle Patologie Emergenti, Policlinico Universitario, Palermo, Italy
Ada Maria Florena, Istituto di Anatomia ed Istologia Patologica, Policlinico Universitario, Palermo, Italy
Melchiorre Cervello, Istituto di Biomedicina ed Immunologia Molecolare, C.N.R., Palermo, Italy
Natale D’Alessandro, Dipartimento di Scienze Farmacologiche, Policlinico Universitario, Palermo, Italy
Author contributions: All authors contributed equally to the work.
Supported by: grant from Ministero dell’Istruzione, dell’Università e della Ricerca year 2004 (to GM)
Correspondence to: Professor Giuseppe Montalto, Cattedra di Medicina Interna, via del Vespro 127, 90143 Palermo, Italy. gmontal@unipa.it
Telephone: +39-91-6552991 Fax: +39-91-6552936
Received: August 10, 2005
Revised: September 5, 2005
Accepted: September 15, 2005
Published online: April 28, 2006

AIM: To evaluate the immunohistochemical localization of interleukin-6 (IL-6) and IL-6 receptor (IL-6R) on tumor tissue specimens from patients with hepatocellular carcinoma (HCC) and the serum levels of IL-6 and sIL-6R in a group of patients with HCC as well as liver cirrhosis (LC) in a group of patients with LC alone and in a control group.

METHODS: Three groups of subjects were studied: group I (n = 83) suffering from HCC and LC, group II (n = 72) suffering from LC alone and group III (n = 42) as healthy controls. All patients had hepatitis C virus infection. Serum IL-6 and IL-6R levels were determined using a commercially available ELISA kit. Immunohistochemistry was performed using the streptavidin-biotin complex and rabbit polyclonal antibodies against IL-6 and IL-6R.

RESULTS: Immunohistochemistry analysis showed a medium to strong cytoplasmic and membrane reactivity for IL-6 and IL-6R respectively, in at least 40% of cases of HCC, whereas liver cirrhosis patients and controls were negative for IL-6 or showed a very mild and focal dot-like cytoplasmic reaction for IL-6R. Serum IL-6 levels in HCC group were significantly higher than those in LC and control groups (P < 0.0001). There was no significant difference in sIL-6R concentrations among 3 groups. When the patients with HCC were divided into groups according to Okuda’s classification, a significant serum increase of IL-6 and sIL-6R level was observed from stage I to stage III (P < 0.02, P < 0.0005). When HCC and LC patients were divided into 3 classes of cirrhosis severity according to Child-Pugh, values in HCC patients were significantly higher than those in LC patients for each corresponding class (P < 0.01).

CONCLUSION: IL-6 serum levels in HCC patients are higher than those in LC patients and controls, suggesting an increased production of this cytokine by neoplastic cells. sIL-6R values are similar in all groups, increasing only in stage III HCC patients. These data suggest that they have a closer relationship with the neoplastic mass rather than with the residual functioning hepatic mass.

Keywords: Interleukin-6, Cytokine, Chronic liver disease, Immunohistochemistry