Profile of circulating levels of interleukin-1 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 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.
Ito
H
H
Dept. of Surgery II, Mie University Medical School, Tsu, Japan.
Miki
C
C
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D014408:Biomarkers, Tumor / Q000032:analysis / Q000097:blood*; D016022:Case-Control Studies; D015179:Colorectal Neoplasms / Q000097:blood* / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D015850:Interleukin-6 / Q000032:analysis / Q000097:blood*; D008113:Liver Neoplasms / Q000556:secondary; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000097:blood; D009367:Neoplasm Staging; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors*; D012044:Regression Analysis
D014408:Biomarkers, Tumor; D015850:Interleukin-6; D009363:Neoplasm Proteins; D017472:Receptors, Interleukin-1; C030193:immunosuppressive acidic protein