Interferon-gamma 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/m2 to patients with cancer induces easily measurable serum interferon-gamma levels of 1 to 500 U/ml. After a lag of 1 h, interferon-gamma rises 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-gamma fourfold, but does not diminish the lag period. Peak levels of interferon-gamma are also increased by concurrent administration of interferon-beta with interleukin-2. Continuous i.v. infusion of 1.5 to 20 MIU/m2 of interleukin-2/day results in interferon-gamma levels of 1 to 7 U/ml. Hypotension, which is characteristically associated with interleukin-2 administration, is correlated with interferon-gamma levels in only some patients. There was no apparent correlation between tumor regression and serum interferon-gamma levels.
Konrad
M W
MW
de Vlaminck Institute, Lafayette, California.
DeWitt
S K
SK
Bradley
E C
EC
Goodman
G
G
Groves
E C
EC
Hersh
E M
EM
Krigel
R L
RL
Rudolph
A
A
D001794:Blood Pressure / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007262:Infusions, Intravenous; D007275:Injections, Intravenous; D007369:Interferon Inducers / Q000494:pharmacology*; D007371:Interferon-gamma / Q000096:biosynthesis* / Q000097:blood; D007376:Interleukin-2 / Q000494:pharmacology*; D007700:Kinetics; D009369:Neoplasms / Q000188:drug therapy*; D011863:Radioimmunoassay; D011994:Recombinant Proteins / Q000008:administration & dosage
D007369:Interferon Inducers; D007376:Interleukin-2; D011994:Recombinant Proteins; D007371:Interferon-gamma