Rapid cytokine release in cancer patients treated with interleukin-2

J Immunother (1991). 1992 Aug;12(2):123-31. doi: 10.1097/00002371-199208000-00007.

Abstract

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)

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinoma, Renal Cell / immunology
  • Carcinoma, Renal Cell / therapy
  • Cytokines / blood
  • Cytokines / metabolism*
  • Humans
  • Immunotherapy
  • Infusions, Intravenous
  • Interferon-gamma / metabolism
  • Interleukin-2 / administration & dosage
  • Interleukin-2 / blood
  • Interleukin-2 / therapeutic use*
  • Interleukin-6 / metabolism
  • Kidney Neoplasms / immunology
  • Kidney Neoplasms / therapy
  • Kinetics
  • Melanoma / immunology
  • Melanoma / therapy
  • Neoplasms / immunology
  • Neoplasms / therapy*
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Cytokines
  • Interleukin-2
  • Interleukin-6
  • Tumor Necrosis Factor-alpha
  • Interferon-gamma