Profile of circulating levels of interleukin-l receptor antagonist and interleukin-6 in colorectal cancer patients

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 interleukin-1 receptor an tagonist (IL-1ra) and IL-6 in 80 colorectal cancer patients and tissue conc entrations of IL-1ra and IL-6 in 60 primary colorectal cancers and normal c olonic mucosas were determined. The serum concentration of immunosuppressiv e acidic protein (IAP) was also determined. Results: The serum concentratio ns 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 asso ciated with clinicopathologic factors including tumor size, liver metastasi s, lymph node metastasis, vessel involvement, or serum level of carcinoembr yonic antigen. Although the serum IL-1ra level increased in keeping with th e increase of serum IL-6, the net balance between IL-1ra and IL-6 was signi ficantly lower than that in the controls. The serum IL-1ra to IL-6 ratio de creased in association with the patient's age, the rate of loss of body wei ght and the serum level of LAP. Although the serum level of IL-6 correlated with the IL-6 concentration in the cancer tissue, the serum level of IL-1r a did not correlate with the IL-1ra concentration in this tissue. Conclusio ns: Serum IL-1ra, induced systemically by a marked activation of the IL-6 n etwork in cancer tissue, may be a potent index that evaluates disease progr ession of colorectal carcinoma. Decreased serum IL-1ra to IL-6 ratio may re flect the deterioration of the systemic anti-inflammatory response that is associated with aging, tumor-related malnutrition, or immunosuppression.