Interleukin-1 beta induces interleukin-1 receptor antagonist and tumor necrosis factor binding protein in humans.
Sustained release or high levels of interleukin-1 (IL-1) and/or tumor necrosis factor (TNF), as observed after endotoxin challenge, can produce a variety of toxicities. Naturally occurring inhibitors to IL-1 and TNF, IL-1 receptor antagonist (IL-1ra) and soluble TNF receptor forms, have been detected. These proteins may function to buffer or limit the effects of these cytokines as part of a regulatory network. As part of a clinical trial of recombinant human interleukin-1 beta (rhIL-1 beta), serial plasma samples were obtained from 6 patients with metastatic melanoma treated with 30-min infusions of rhIL-1 beta for 5 consecutive days. The presence of circulating IL-1 receptor antagonist and soluble TNF binding proteins (TNF-R55-BP and TNF-R75-BP) were assessed. A maximum 86-fold increase for IL-1ra, a 7-8-fold increase for TNF-R55-BP, and a 2-3-fold increase for TNF-R75-BP were seen 2-4 h, 1 h, and 4 h, respectively, after rhIL-1 beta infusion. On each day of the treatment, the secretion of IL-1ra and release of TNF-R55-BP was observed, but there was no accumulation above baseline value for IL-1ra before each of the 5 daily infusions. Although there was a steady decrease of the 6-h postinfusion plasma levels for IL-1ra and TNF-R55-BP over the 5 treatment days, no increase of clinical side effects was noted. Two patients had measurable levels of TNF-alpha, but no correlation to TNF-binding proteins was observed. Our data show that early after rhIL-1 beta infusion the induction of IL-1ra secretion, as well as TNF-binding protein release, is observed.
Division of Oncology, Stanford University Medical Center, California 94305-5306.
M J
MJ
Bargetzi
M
M
Lantz
C G
CG
Smith
F M
FM
Torti
I
I
Olsson
S P
SP
Eisenberg
H F
HF
Starnes
D000328:Adult; D000368:Aged; D005260:Female; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D008297:Male; D008545:Melanoma / Q000097:blood* / Q000628:therapy; D008875:Middle Aged; D011956:Receptors, Cell Surface / Q000032:analysis*; D018124:Receptors, Tumor Necrosis Factor; D012795:Sialoglycoproteins / Q000097:blood*; D013997:Time Factors
C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D011956:Receptors, Cell Surface; D018124:Receptors, Tumor Necrosis Factor; D012795:Sialoglycoproteins