The neuroendocrine effects of interleukin-2 treatment.
Observations of neuropsychiatric changes in patients receiving interleukin-2 (IL-2) led us to examine the effects of IL-2 administration on the stress-related hormones, beta-endorphin, ACTH, cortisol, and CRH. We evaluated 30 cancer patients who received immunotherapy with IL-2 or IL-2 plus lymphokine-activated killer (LAK) cells. Blood samples were taken immediately before and 4 and 8 h after infusion of IL-2 or IL-2 plus LAK cells. IL-2 stimulated increased hormone levels 4 h after infusion compared with those before therapy and with basal levels in normal volunteers at the following magnitudes: beta-endorphin, 10-fold; ACTH, 20-fold; and cortisol, 2-fold. The effect of IL-2 was not altered in patients also receiving LAK cells. An effect of treatment course was noted, with higher stimulated values seen 4 h after IL-2 in the second treatment course compared with those after the first course [change (delta) in beta-endorphin, 101 vs. 11 fmol/mL; delta ACTH, 138 vs. 8 pmol/L; delta cortisol, 414 vs. 218 nmol/L]. We conclude that IL-2 treatment induces the release of neuroendocrine hormones and that a significant increase in hormonal stimulation occurs upon reexposure to IL-2.
Denicoff
K D
KD
Biological Psychiatry Branch, National Institute of Mental Health, Bethesda, Maryland 20892.
Durkin
T M
TM
Lotze
M T
MT
Quinlan
P E
PE
Davis
C L
CL
Listwak
S J
SJ
Rosenberg
S A
SA
Rubinow
D R
DR
D000324:Adrenocorticotropic Hormone / Q000097:blood; D003346:Corticotropin-Releasing Hormone / Q000097:blood; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007376:Interleukin-2 / Q000097:blood / Q000276:immunology / Q000627:therapeutic use*; D007694:Killer Cells, Natural / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000628:therapy*; D009490:Neurosecretory Systems / Q000187:drug effects* / Q000378:metabolism; D011994:Recombinant Proteins / Q000627:therapeutic use; D001615:beta-Endorphin / Q000097:blood
D007376:Interleukin-2; D011994:Recombinant Proteins; D001615:beta-Endorphin; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone; D006854:Hydrocortisone