Production of interleukin-1-receptor antagonist during experimental endotoxaemia.
Interleukin-1 (IL-1) has been implicated in the pathogenesis of sepsis. IL-1-receptor antagonist (IL-1ra) is a naturally occurring inhibitor of IL-1 activity that competes with IL-1 for occupancy of cell-surface receptors but possesses no agonist activity. We induced endotoxaemia in 9 healthy human volunteers by injection of Escherichia coli endotoxin, and measured plasma concentrations of IL-1 and IL-1ra by radioimmunoassay during the next 24 h. Peak plasma concentrations of IL-1ra were about a hundred-fold greater than those of IL-1 beta. No IL-1 or IL-1ra were detectable in the plasma of 4 volunteers injected with saline. Our results suggest that the predominant natural response to endotoxin in man is the production of antagonist rather than agonist.
Department of Medicine, New England Medical Centre, Tufts University School of Medicine, Boston, Massachusetts 02111.
E V
EV
Granowitz
A A
AA
Santos
D D
DD
Poutsiaka
J G
JG
Cannon
D W
DW
Wilmore
S M
SM
Wolff
C A
CA
Dinarello
D000293:Adolescent; D000328:Adult; D004731:Endotoxins / Q000097:blood / Q000494:pharmacology*; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000032:analysis / Q000037:antagonists & inhibitors*; D008297:Male; D008875:Middle Aged; D014176:Protein Biosynthesis; D011506:Proteins / Q000032:analysis; D011971:Receptors, Immunologic / Q000037:antagonists & inhibitors*; D017472:Receptors, Interleukin-1; D012795:Sialoglycoproteins; D013997:Time Factors
D004731:Endotoxins; C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D011506:Proteins; D011971:Receptors, Immunologic; D017472:Receptors, Interleukin-1; D012795:Sialoglycoproteins; C044101:endotoxin, Escherichia coli