Elevated levels of shed type II IL-1 receptor in sepsis. Potential role for type II receptor in regulation of IL-1 responses.
Two types of cellular IL-1Rs have been characterized and cloned from both human and murine sources. The type II IL-1R has a very short cytoplasmic domain and does not seem to participate in IL-1 signaling. We demonstrate that type II IL-1Rs are released from the surface of neutrophils in response to treatment with TNF or endotoxin. In addition, serum from patients with sepsis syndrome contains elevated levels of soluble type II IL-1Rs. Neutrophils isolated from patients with sepsis have greatly enhanced expression of type II IL-1R mRNA and cell surface receptors and are therefore a likely source for the shed receptors in serum. Of the three forms of IL-1, soluble type II IL-1R binds IL-1 beta with highest affinity and also selectively inhibits IL-1 beta activity. We propose that increased cell surface expression and rapid release of preformed type II IL-1R from neutrophils, as a soluble IL-1 beta binding protein, represents a mechanism that has evolved for regulating IL-1 activity in sepsis.
Giri
J G
JG
Immunex Research and Development Corporation, Seattle, WA 98101.
Wells
J
J
Dower
S K
SK
McCall
C E
CE
Guzman
R N
RN
Slack
J
J
Bird
T A
TA
Shanebeck
K
K
Grabstein
K H
KH
Sims
J E
JE
D015152:Blotting, Northern; D002460:Cell Line; D004731:Endotoxins / Q000494:pharmacology; D005434:Flow Cytometry; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000378:metabolism*; D009504:Neutrophils / Q000276:immunology; D011233:Precipitin Tests; D017472:Receptors, Interleukin-1 / Q000096:biosynthesis* / Q000737:chemistry* / Q000502:physiology; D018805:Sepsis / Q000276:immunology*; D012795:Sialoglycoproteins / Q000378:metabolism; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D004731:Endotoxins; C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D017472:Receptors, Interleukin-1; D012795:Sialoglycoproteins; D014409:Tumor Necrosis Factor-alpha