Detection of interferon inhibitors or antagonists in gastrointestinal malignancies.

BACKGROUND/AIMS: The aim of this study was to investigate the IFN-inhibiting activity in sera from patients with gastrointestinal malignancies, exerted in a variety of cellular types, as well as to elucidate the determinants of cellular sensitivity to such IFN-inhibitors.

METHODOLOGY

Sera from 16 patients with gastric cancer and 18 with colon cancer were tested, while sera from 37 healthy blood donors were used as controls. All serum samples, collected before any kind of treatment, were tested for IFN-blocking and endogenous IFN-like activity. These activities were determined by assaying the inhibition of the vesicular stomatitis virus specific cytopathic effect in three cell lines: A549 cells, intestine 407 and Chang liver cells.

RESULTS

There was no endogenous IFN in any of the serum samples of patients or controls. Concerning the IFN blocking activity of serum, there was no significant difference between gastric and colon cancer, while a marked variability was prominent depending on the cell line used. 76.4% of serum samples exerted IFN-blocking activity in the A549 cells, 47.05% in the Int-407 cell line and 32.3% in the Chang Liver cells. No control sample had IFN-blocking activity in any of the cell lines tested.

CONCLUSIONS

The results support a cytokine and cytokine inhibitors network, mediating pathophysiological events at the cellular level as well as the whole organism. The limited responsiveness of many neoplasias, including digestive system cancer, to IFN treatment might be due to the presence of IFN inhibitors in the patient's serum.