Induction of circulating soluble tumour necrosis factor receptor and interleukin 1 receptor antagonist following interleukin 1 alpha infusion in humans.
The aim of this study was to investigate circulating levels of tumour necrosis factor soluble receptor p55 (TNFsrp55) and interleukin 1 receptor antagonist (IL-1ra) in cancer patients undergoing treatment with IL-1 alpha. Patients were treated with 0.03 micrograms/kg IL-1 alpha administered intravenously over a 30 min interval daily for five consecutive days. Plasma TNFsrp55 levels rose dramatically and peaked (24.5 +/- 3.6 ng/ml) within 1 h after the first IL-1 alpha infusion. Thereafter, the levels rapidly declined and reached baseline levels within 24 h. The increases observed on days 3 and 5 of treatment were less pronounced but the reductions in peak levels were not statistically significant. IL-1ra levels increased less abruptly after an IL-1 alpha infusion than did TNFsrp55 levels and peaked (25.3 +/- 5.1 ng/ml) within 2 h of the start of the IL-1 alpha infusion. Levels then rapidly declined reaching baseline values within 24 h. As with TNFsrp55 levels, peak IL-1ra levels observed on days 3 and 5 of treatment were less than those measured on day 1. IL-1 alpha and IL-1 beta levels were consistently below the threshold of detection of the RIAs employed in these studies. Likewise, with the exception of a single time point in one of the four patients studied, TNF-alpha was undetectable in all plasma samples assayed.(ABSTRACT TRUNCATED AT 250 WORDS)
Tilg
H
H
Department of Medicine, New England Medical Center, Boston, MA 02111.
Trehu
E
E
Shapiro
L
L
Pape
D
D
Atkins
M B
MB
Dinarello
C A
CA
Mier
J W
JW
D003520:Cyclophosphamide / Q000627:therapeutic use / Q000633:toxicity*; D006801:Humans; D007262:Infusions, Intravenous; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000008:administration & dosage / Q000627:therapeutic use / Q000633:toxicity*; D007700:Kinetics; D009369:Neoplasms / Q000097:blood / Q000628:therapy*; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors; D018124:Receptors, Tumor Necrosis Factor / Q000096:biosynthesis* / Q000378:metabolism; D012795:Sialoglycoproteins / Q000096:biosynthesis* / Q000097:blood; D013997:Time Factors
C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D017472:Receptors, Interleukin-1; D018124:Receptors, Tumor Necrosis Factor; D012795:Sialoglycoproteins; D003520:Cyclophosphamide