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-a in patients treated with recombinant interferon-γ and 2) to relate changes in TNF serum levels to other biological responses observed during treatment with interferon gamma (IFN-γ). Patients: Five patients suffering from metastasizing renal cell carcinoma. Intervention: Each patient received three treatment cycles of 10 μg, 100 μg and 500 μg IFN-γ 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-α), IFN-γ 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-γ. Results indicated that elevated serum levels of TNF-α are induced by 100 Itg and 500 Itg IFN-γ. 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-γ serum levels. © 1990, Gustav Fischer Verlag · Stuttgart · New York. All rights reserved.