Profile of Circulating Levels of Interleukin-1 Receptor Antagonist and Interleukin-6 in Colorectal Cancer Patients

Abstract

Background: Circulating levels of pro-inflammatory cytokines are associated with the disease status of cancer patients. We investigated the profile of circulating levels of interleukin (IL)-6 and its antagonist in colorectal cancer patients. Methods: Serum concentrations of interkeukin-1 receptor antagonist (IL-1ra) and IL-6 in 80 colorectal cancer patients and tissue concentrations of IL-1ra and IL-6 in 60 primary colorectal cancers and normal colonic mucosas were determined. The serum concentration of immunosuppressive acidic protein (IAP) was also determined. Results: The serum concentrations of IL-1ra and IL-6 in the patients were significantly higher than those in the controls. The serum concentration of IL-1ra in the patients was associated with clinicopathologic factors including tumor size, liver metastasis, lymph node metastasis, vessel involvement, or serum level of carcinoembryonic antigen. Although the serum IL-1ra level increased in keeping with the increase of serum IL-6, the net balance between IL-1ra and IL-6 was significantly lower than that in the controls. The serum IL-1ra to IL-6 ratio decreased in association with the patient's age, the rate of loss of body weight and the serum level of IAP. Although the serum level of IL-6 correlated with the IL-6 concentration in the cancer tissue, the serum level of IL-1ra did not correlate with the IL-1ra concentration in this tissue. Conclusions: Serum IL-1ra, induced systemically by a marked activation of the IL-6 network in cancer tissue, may be a potent index that evaluates disease progression of colorectal carcinoma. Decreased serum IL-1ra to IL-6 ratio may reflect the deterioration of the systemic anti-inflammatory response that is associated with aging, tumor-related malnutrition, or immunosuppression.