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Autoreactivity against interleukin 6 as a risk factor in elderly patients with colorectal carcinoma
1Second Department of Surgery, Mie University School of Medicine, Edobashi 2-174, Tsu, Mie 514-8507, Japan.
Hypothesis:
Aging results in both decreased immunity to exogenous antigens and increased autoreactivity. We suggest that the increased autoreactivity against tumor-releasing cachectic cytokine and postsurgical hypercytokinemia are involved in the cause of increased morbidity and mortality in elderly patients with colorectal cancer.
Design, Setting, And Patients:
Eighty-three patients with colorectal cancer admitted to a university hospital were studied prospectively.
Interventions:
Surgical specimens of primary colorectal cancer were harvested and peripheral venous blood samples were obtained perioperatively.
Main Outcome Measures:
The tissue concentrations of interleukin (IL) 1beta and IL-6 were determined. Serial determinations of serum concentrations of IL-6, IL-6 soluble receptor, and C-reactive protein were performed. Nutritional status was assessed by the creatinine height index.
Results:
The tumor IL-6 content was the independent factor that influenced the creatinine height index in the elderly patients, whereas Dukes classification was the only independent factor that influenced the creatinine height index in the younger patients. The elderly patients showed an exaggerated C-reactive protein response and increased IL-6 soluble receptor consumption independent of the tumor IL-6 content and postoperative IL-6 response. This immunologic disturbance was followed by a significant (P = .03) delay in the normalization of activated neutrophils, which seemed to be associated with postoperative fatal complications in the elderly patients.
Conclusions:
Autoreactivity against intrinsic IL-6 was increased and seemed to be associated with poor clinical outcomes in elderly patients. To prevent fatal complications, adequate nutritional support early in treatment and attenuation of the neutrophil-related hyperinflammatory sequence by controlling the IL-6 soluble receptor affinity should be advocated.