Objective: To evaluate the clinical significance of preoperative serum levels of interleukin-10 (IL-10) and interleukin-6 (IL-6) in patients with resectable hepatocellular carcinoma (HCC).
Summary Background Data: IL-10 is an immunosuppressive factor and IL-6 is a multifunctional cytokine that plays a role in host defense mechanisms. Both have been reported to be related to the disease prognosis in some human solid tumors. Their role in human HCC has not been investigated.
Methods: Preoperative serum samples of 67 patients with HCC who underwent potentially curative resection and 27 normal healthy donors were assayed. Levels of IL-10 and IL-6 were determined by enzyme-linked immunosorbent assay. The clinical significance of serum IL-10 and IL-6 was evaluated and compared with conventional clinicopathologic factors.
Results: Levels of IL-10 and IL-6 were significantly higher in patients with HCC than in healthy subjects. There was no correlation between IL-10 and IL-6 levels. Tumor resection resulted in a decrease in IL-10 and IL-6 levels. On univariate analysis, patients with high IL-10 levels had a worse disease-free survival, but IL-6 levels had no correlation with the disease-free survival. Multivariate analysis identified IL-10 levels as a predictor of postresectional outcome, in addition to the well-established clinical risk factors.
Conclusions: In patients with HCC, the preoperative serum IL-10 level is related to the clinical outcome. IL-10 may play an important role in the progression of HCC.
Hepatocellular carcinoma (HCC) is a common malignancy that often occurs in patients with chronic liver disease, usually resulting from type B or C virus infection. Although surgical resection is an effective treatment for the disease, the rate of tumor recurrence after resection is high. 1 Occult microscopic intrahepatic or extrahepatic metastasis and background factors of the diseased liver, including active inflammation, 2,3 had been regarded as significant risk factors for tumor recurrence.
Interleukin-10 (IL-10) is a pleiotropic cytokine produced by macrophages, T-helper 2 cells, and B lymphocytes (CD5 subset) and can both stimulate and suppress the immune response. 4 IL-10 has been shown to inhibit various immune functions, such as antigen presentation, cytokine production, macrophage activation, and antigen-specific T-cell proliferation. By interfering with the costimulatory function of antigen-presenting cells (e.g., downregulation of class II MHC expression of monocytes and costimulatory molecule expression of macrophages), IL-10 reduces antigen-specific T-cell proliferation. Recently, it has been proposed that IL-10 plays a key role in the oncogenetic and metastatic ability of neoplasms, 5,6 and increased levels have been found in the plasma of patients with different histotypes of solid and hematopoietic tumors. 7-9
Interleukin-6 (IL-6), a multifunctional cytokine produced by a range of cells, plays a central role in host defense mechanisms. 10 Recently, it was shown that IL-6 is produced by human epidermal cells and epidermoid carcinoma cell lines, 11 as well as other epithelial tumors, including bladder carcinoma, 12 renal cell carcinoma, 13 and ovarian cancer. 14 Increased serum IL-6 levels have been found in patients with multiple myeloma, 15 renal cell carcinoma, 16 bladder carcinoma, 17 head and neck cancer, 18 ovarian cancer, 19 and cholangiocarcinoma. 20
Serum IL-10 levels have been observed to be significantly elevated in patients with type C chronic liver disease, and IL-10 may be related to the development of HCC. 21 High serum IL-6 levels had been observed in patients with advanced HCC. 22 However, it is not known whether serum levels of IL-10 and IL-6 are related to the prognosis of patients with relatively early and resectable disease. The present study was designed to investigate the serum level of IL-10 and IL-6 in patients with resectable HCC, to determine whether human hepatoma cell lines can produce IL-10 and IL-6 in vitro, and to elucidate the possible role of IL-10 and IL-6 in tumor biology and their prognostic impact.