Circulating interleukin 6 concentrations and insulin resistance in patients with cancer.

The mechanism of insulin resistance in patients with cancer is not clear. This study was conducted to evaluate the possible role of circulating cytokines in inducing insulin resistance in patients with cancer. Twenty-three patients with a variety of cancers were studied, including one patient with oesophageal cancer, 12 with gastric cancer, four with colon cancer and six with lung cancer. Six normal volunteers served as controls. Insulin resistance was evaluated by euglycaemic hyperinsulinaemic glucose clamp with a high physiological insulin concentration of 100 microunits/ml. Metabolized glucose, the M value, was compared between patients with cancer and controls. Serum concentrations of interleukin (IL) 6 and other cytokines (tumour necrosis factor (TNF) alpha, IL-8 and IL-10) were measured by enzyme-linked immunosorbent assay. The mean(s.d.) M value for patients with cancer (5.47(1.59) mg per kg per min) was significantly lower than that for controls (8.23(0.79) mg per kg per min) (P< 0.001). There was no relationship between the M value and degree of body-weight loss. Serum IL-6 concentration was measurable in eight of 23 patients: four with lung cancer, two with gastric cancer, and one each with oesophageal and colon cancer. None of the controls had a measurable serum IL-6 concentration. There was no significant relationship between serum IL-6 concentration and body-weight loss. TNF-alpha was undetectable in the serum of both patients with cancer and controls. Serum IL-8 and IL-10 were detected in seven and one of 23 patients respectively. These cytokines were not detected in the serum of controls. The M value was significantly smaller in those with measurable serum IL-6 (4.01(1.22) mg per kg per min) than in those with no measurable IL-6 (6.26(1.16) mg per kg per min) (P< 0.001). IL-6 and IL-8 levels were raised more frequently in the same patient but there was no significant relationship between IL-8 and M values. These results may suggest that IL-6 is related to insulin resistance in patients with cancer.