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.
Granowitz
E V
EV
Department of Medicine, New England Medical Centre, Tufts University School of Medicine, Boston, Massachusetts 02111.
Santos
A A
AA
Poutsiaka
D D
DD
Cannon
J G
JG
Wilmore
D W
DW
Wolff
S M
SM
Dinarello
C A
CA
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