Endocrine effects of IL-1 alpha and beta administered in a phase I trial to patients with advanced cancer.
Previous primate and rodent studies suggested that interleukin-1 alpha (IL-1 alpha) caused changes in the secretion of pituitary, adrenal, thyroid, and gonadal hormones, as well as acute-phase reactants. Plasma samples were obtained after IL-1 alpha and beta treatment in cancer patients to document the changes in endocrine function suggested by the animal models. Successive groups of patients were treated at IL-1 alpha doses of 0.01, 0.03, 0.1, 0.3, and 1.0 microgram/kg, given daily as a 15-min intravenous bolus. IL-1 beta was given at 0.1 microgram/kg by the same route and time course. After the first dose of IL-1, statistically significant elevations of a.m. and p.m. cortisol, growth hormone (GH), and prolactin (PRL) occurred. Thyroid-stimulating hormone (TSH) and C-reactive protein (CRP) were elevated by the sixth treatment day. Testosterone decreased significantly in male patients. Follicle-stimulating hormone (FSH) and luteinizing hormone (LH) were more variable but decreased in most patients. The changes in cortisol, GH, PRL, TSH, CRP, FSH, LH, and testosterone resolved after treatment and did not result in clinically apparent endocrinopathies. Bolus doses of IL-1 alpha and beta cause significant changes in many endocrine laboratory parameters and influence the in vivo activities of multiple homeostatic endocrine functions in human beings.
Curti
B D
BD
Biological Response Modifiers Program, NCI-FCRDC, Frederick, MD 21701, USA.
Urba
W J
WJ
Longo
D L
DL
Janik
J E
JE
Sharfman
W H
WH
Miller
L L
LL
Cizza
G
G
Shimizu
M
M
Oppenheim
J J
JJ
Alvord
W G
WG
Smith
J W
JW
D000209:Acute-Phase Proteins / Q000187:drug effects; D000324:Adrenocorticotropic Hormone / Q000187:drug effects; D004702:Endocrine Glands / Q000187:drug effects* / Q000378:metabolism*; D005260:Female; D005640:Follicle Stimulating Hormone / Q000378:metabolism; D019382:Human Growth Hormone / Q000187:drug effects; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007375:Interleukin-1 / Q000009:adverse effects* / Q000627:therapeutic use; D007986:Luteinizing Hormone / Q000187:drug effects; D008297:Male; D009369:Neoplasms / Q000503:physiopathology / Q000628:therapy*; D011388:Prolactin / Q000187:drug effects; D013739:Testosterone / Q000378:metabolism; D013961:Thyroid Gland / Q000187:drug effects
D000209:Acute-Phase Proteins; D007375:Interleukin-1; D019382:Human Growth Hormone; D013739:Testosterone; D000324:Adrenocorticotropic Hormone; D011388:Prolactin; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; D006854:Hydrocortisone