Induction of soluble tumour necrosis factor receptors during treatment with interleukin-2.
Interleukin-2 (IL-2) treatment induces other cytokines such as tumour necrosis factor (TNF) TNF may mediate some of the anti-tumour activity of IL-2, but conversely, may contribute to its dose limiting toxicities. Cleaved extracellular domains of the p55 and the p75 TNF receptors (sTNF-R1 and R2) bind to and inhibit the biological activity of TNF in vitro, but may also act as carrier molecules. We have assayed TNF and sTNFR-1 and 2 in the plasma of advanced cancer patients, before and during treatment with IL-2. Plasma levels of TNF in 22 patients were not significantly different from 25 normal controls, but levels of sTNFR-1 and sTNFR-2 were higher (P < 0.001). Levels of TNF and both its soluble receptors were significantly increased in 13 patients receiving IL-2 therapy. Maximum induced levels of sTNFR-1 and sTNFR-2 correlated closely with maximum induced levels of TNF (P < 0.001), but peak levels of sTNFR-1 and two were achieved 24-48 h after peak TNF. Levels of TNF and sTNF-Rs did not correlate with toxicity. Treatment with IL-2 leads not only to induction of TNF but also soluble binding proteins at levels which may modulate its biological activity.
Miles
D W
DW
Imperial Cancer Research Fund Clinical Oncology Unit, Guy's Hospital, London, UK.
Aderka
D
D
Engelmann
H
H
Wallach
D
D
Balkwill
F R
FR
D001943:Breast Neoplasms / Q000097:blood / Q000628:therapy; D002292:Carcinoma, Renal Cell / Q000097:blood / Q000628:therapy; D004334:Drug Administration Schedule; D006801:Humans; D007376:Interleukin-2 / Q000627:therapeutic use*; D007680:Kidney Neoplasms / Q000097:blood / Q000628:therapy; D008545:Melanoma / Q000097:blood / Q000628:therapy; D011956:Receptors, Cell Surface / Q000032:analysis / Q000096:biosynthesis*; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000096:biosynthesis*
D007376:Interleukin-2; D011956:Receptors, Cell Surface; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha