Interferon-γ induced by administration of recombinant interleukin-2 to patients with cancer: Kinetics, dose dependence, and correlation with physiological and therapeutic response

The administration of recombinant interleukin-2 as an i.v. bolus at dose levels of from 1 to 30 MIU/m²to patients with cancer induces easily measurable serum interferon-γ levels of 1 to 500 U/ml. After a lag of 1 h, interferon-^γrises to a maximum at 4 h and then slowly decreases. The peak values are poorly correlated with the dose of interleukin-2, and thus must be also be dependent on other factors. Successive administration of interleukin-2 typically increases the peak level of interferon-^γfourfold, but does not diminish the lag period. Peak levels of interferon-γ are also increased by concurrent administration of interferon-β with interleukin-2. Continuous i.v. infusion of 1.5 to 20 MIU/m²of interleukin-2/day results in interferon-^γlevels of 1 to 7 U/ml. Hypotension, which is characteristically associated with interleukin-2 administration, is correlated with interferon-^γlevels in only some patients. There was no apparent correlation between tumor regression and serum interferon-^γlevels.