Influence of IL-1 receptor blockade on the human response to endotoxemia.
Although the experimental administration of IL-1 induces several aspects of the inflammatory response, such as fever, tachycardia, and acute phase proteinemia, the contribution of IL-1 to the human responses to injury or infection remains unclear. A specific IL-1R antagonist (IL-1ra), which effectively blocks the actions of IL-1, was utilized to evaluate the influence of endogenous IL-1 during experimental human endotoxemia. Eighteen healthy volunteers each underwent one control study day, followed 3 days later by one of three randomly chosen treatments: a 6-h infusion of IL-1ra alone (133 mg/h), 20 U/kg national reference endotoxin alone, or both endotoxin and IL-1ra infusion. IL-1ra administration alone was not associated with any observable response. Despite achieving high circulating levels of IL-1ra (34 +/- 3 micrograms/ml), there were no significant differences in hemodynamic parameters, core temperature, or resting energy expenditure in those endotoxemic volunteers receiving IL-1ra when compared with those who did not. Furthermore, leukocyte kinetic and circulating cytokine, acute phase protein, and endocrine responses were similar in both endotoxemic groups. However, IL-1 blockade did significantly reduce the subjective severity of symptoms experienced by the endotoxemic volunteers (p < 0.05). This study demonstrates that an endogenous IL-1 response does not play a significant role in the hemodynamic, immunologic, and metabolic responses to mild endotoxemia in humans.
Van Zee
K J
KJ
Department of Surgery, New York Hospital-Cornell Medical Center, NY 10021.
Coyle
S M
SM
Calvano
S E
SE
Oldenburg
H S
HS
Stiles
D M
DM
Pribble
J
J
Catalano
M
M
Moldawer
L L
LL
Lowry
S F
SF
D000324:Adrenocorticotropic Hormone / Q000097:blood; D000328:Adult; D002097:C-Reactive Protein / Q000378:metabolism; D002395:Catecholamines / Q000097:blood; D016207:Cytokines / Q000097:blood; D004731:Endotoxins; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000502:physiology*; D008297:Male; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors*; D012795:Sialoglycoproteins / Q000493:pharmacokinetics / Q000494:pharmacology*; D014115:Toxemia / Q000097:blood / Q000276:immunology*
D002395:Catecholamines; D016207:Cytokines; D004731:Endotoxins; C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D017472:Receptors, Interleukin-1; D012795:Sialoglycoproteins; D000324:Adrenocorticotropic Hormone; D002097:C-Reactive Protein; D006854:Hydrocortisone