Interleukin-1 mediates increased plasma levels of eicosanoids and cytokines in patients with sepsis syndrome.
The purpose of this was to study evaluate the effects of interleukin-1 (IL-1) inhibition by human recombinant IL-1 receptor antagonist (IL-1ra) on plasma prostaglandin, leukotriene, and cytokine levels in sepsis syndrome. As part of a multisite, prospective, randomized, double-blind, placebo-controlled clinical trial, 19 septic patients received IL-1ra in a 100 mg bolus followed by 2.0 mg/kg/h i.v. for 72 h (n = 10) or placebo (n = 9). Plasma thromboxane B2 (TXB2), prostaglandin 6-keto-F1 alpha (PGI), leukotriene B4 (LTB4), leukotrienes C4D4E4 (LTC4D4E4), IL-1 beta, IL-6, and tumor necrosis factor alpha (TNF) were measured by ELISA before study drug infusion (baseline) and at 24, 48, 72, and 96 h after the beginning of the study drug infusion. Differences between placebo and IL-1-ra for plasma LTB4 and TNF were not significant. Plasma TXB2, PGI, LTC4D4E4, and IL-6, expressed as % baseline, were significantly lower in patients receiving IL-1ra than in the placebo group (p < .05), while plasma IL-1 was increased significantly. IL-1 may be a necessary mediator of increased circulating PGI, TXB2, LTC4D4E4, and IL-6 levels in patients with sepsis syndrome. Plasma IL-1 is increased with infusion of IL-1ra. The clinical significance of IL-1 in modifying circulating eicosanoid and cytokine concentrations in clinical sepsis is not clear from the data.
Slotman
G J
GJ
Department of Surgery, Cooper Hospital/University Medical Center, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School at Camden 08103, USA.
Friedman
B
B
Brathwaite
C
C
Mure
A J
AJ
Quinn
J V
JV
Shapiro
E
E
D000293:Adolescent; D000328:Adult; D000368:Aged; D016207:Cytokines / Q000097:blood*; D004311:Double-Blind Method; D015777:Eicosanoids / Q000097:blood*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D053590:Interleukin 1 Receptor Antagonist Protein; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D015203:Reproducibility of Results; D012795:Sialoglycoproteins / Q000627:therapeutic use*; D016019:Survival Analysis; D018746:Systemic Inflammatory Response Syndrome / Q000097:blood* / Q000188:drug therapy; D013997:Time Factors; D016896:Treatment Outcome
D016207:Cytokines; D015777:Eicosanoids; C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D012795:Sialoglycoproteins