Treatment of cancer patients with recombinant interferon-gamma induces release of endogenous tumor necrosis factor-alpha.

STUDY OBJECTIVE

1. to investigate serum levels of tumor necrosis factor-alpha in patients treated with recombinant interferon-gamma and 2) to relate changes in TNF serum levels to other biological responses observed during treatment with interferon gamma (IFN-gamma).

PATIENTS

Five patients suffering from metastasizing renal cell carcinoma.

INTERVENTION

Each patient received three treatment cycles of 10 micrograms, 100 micrograms and 500 micrograms IFN-gamma applied three times at weekly intervals. The treatment cycles were separated by a therapy free interval of two weeks. The order of dose levels was randomly assigned to each patient.

MEASUREMENTS AND MAIN RESULTS

Tumor necrosis factor alpha (TNF-alpha), IFN-gamma and neopterin serum levels, monocyte counts in the peripheral blood and body temperature were measured immediately before and 4, 24, 48, 72, and 168 h after each application of IFN-gamma. Results indicated that elevated serum levels of TNF-alpha are induced by 100 micrograms and 500 micrograms IFN-gamma. Repeated application of the same dose led to downregulation of TNF release into the serum. Changes in TNF serum levels did not correlate with the magnitude of febrile reactions, neopterin production or IFN-gamma serum levels.