IN-VIVO TUMOR-NECROSIS-FACTOR-ALPHA AS INDICATOR OF BIOLOGIC AND CLINICAL-RESPONSE TO LOW-DOSE SC RECOMBINANT INTERLEUKIN-2

The effect of low-dose human recombinant interleukin-2 (rIL-2) on the induction of secondary tumor necrosis factor-alpha (TNF-alpha) in vivo was studied in 16 patients with metastatic renal cell carcinoma. In a ll patients s.c. rIL-2 resulted in a significant increase in TNF-alpha serum levels within 4 to 8 hours, as determined by enzyme-linked immu nosorbent assay (ELISA). TNF-alpha serum concentrations remained eleva ted up to 24 hours following single s.c. administration of rIL-2. Tota l secondary TNF-alpha release, as assessed by the area under the curve (AUC), appeared to be independent of dose distribution of rIL-2 (10 m illion IU rIL-2 q12 hours versus 20 million IU rIL-2 q24 hours). rIL-2 induced TNF-alpha release was significantly higher in patients who ha d received prior rIL-2 immunotherapy, while steroids resulted in a sig nificant suppression of TNF-alpha release. Secondary TNF-alpha release was statistically associated with progression-free survival of renal carcinoma patients and may be a prognostic factor in patients receivin g rIL-2.