Rapid cytokine release in cancer patients treated with interleukin-2.
Serum concentrations of interleukin-2 (IL-2), tumor necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma), interleukin-6 (IL-6), interleukin-1 (IL-1) and interferon-alpha (IFN-alpha) were determined by commercially available enzyme-linked immunosorbent assay (ELISA) or radioimmunoassay (RIA) in cancer patients treated with recombinant IL-2 (rIL-2) either as 1-h infusion (3 or 5 x 10(6)/m2) or continuous intravenous infusion for 5 days (3 x 10(6)/m2/day). A significant increase of TNF-alpha and IL-6 serum levels was observed in each patient. One-hour infusion of IL-2 induced a very rapid secretion of TNF-alpha, IL-6 and IFN-gamma with considerably higher peak levels than during IL-2 continuous intravenous infusion. IFN-gamma was released into the blood of all patients receiving IL-2 1-h infusion, but only occasionally during or after IL-2 continuous intravenous infusion. Neither IFN-alpha nor IL-1 were detectable in the serum before, during, or following IL-2 treatment in all patients studied. The kinetics of IL-2 after 1-h infusion fitted to a two-compartment model, suggesting the synthesis of considerable amounts of endogenous IL-2. Following IL-2 1-h infusion, rising TNF-alpha serum levels preceded the increase of serum IFN-gamma or IL-6. The serum peak levels of IFN-gamma and IL-6 decreased rapidly with a half-life of 0.29 to 2.5 h. The concentration time profiles of TNF following 1-h infusion of IL-2 demonstrated a considerably longer half-life than that of intravenously administered recombinant TNF as done in other studies.(ABSTRACT TRUNCATED AT 250 WORDS)
Weidmann
E
E
Department of Internal Medicine, J.W. Goethe University, Frankfurt/M., Germany.
Bergmann
L
L
Stock
J
J
Kirsten
R
R
Mitrou
P S
PS
D002292:Carcinoma, Renal Cell / Q000276:immunology / Q000628:therapy; D016207:Cytokines / Q000097:blood / Q000378:metabolism*; D006801:Humans; D007167:Immunotherapy; D007262:Infusions, Intravenous; D007371:Interferon-gamma / Q000378:metabolism; D007376:Interleukin-2 / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use*; D015850:Interleukin-6 / Q000378:metabolism; D007680:Kidney Neoplasms / Q000276:immunology / Q000628:therapy; D007700:Kinetics; D008545:Melanoma / Q000276:immunology / Q000628:therapy; D009369:Neoplasms / Q000276:immunology / Q000628:therapy*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D016207:Cytokines; D007376:Interleukin-2; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma