Mortality Benefit of Recombinant Human Interleukin-1 Receptor Antagonist for Sepsis Varies by Initial Interleukin-1 Receptor Antagonist Plasma Concentration*

Abstract

We report a heterogeneous effect of recombinant human interleukin-1 receptor antagonist on 28-day sepsis mortality that is potentially predictable by plasma interleukin-1 receptor antagonist in one trial. A precision clinical trial of recombinant human interleukin-1 receptor antagonist targeted to septic patients with high plasma interleukin-1 receptor antagonist may be worthy of consideration.

α‐Haemolysin production, as a single factor, causes fulminant sepsis in a model ofEscherichia coli‐induced bacteraemia

“…The latter is emphasised by sepsis‐like response being inflicted by direct injection of IL‐1 (Okusawa, Gelfand, Ikejima, Connolly, & Dinarello, ), and patients who survive a severe septic state have higher circulating level of endogenous IL‐1R antagonist (Arnalich et al, ). Although recombinant IL‐1 receptor antagonists have failed to show a general statistically significant beneficial response in clinical trials on septic patients (Fisher, Dhainaut, et al, ; Fisher, Slotman, et al, ; Opal et al, ), newer studies were able to show beneficial effect in patients stratified according to the level of circulating IL‐1R antagonist (Meyer et al, ). Thus, IL‐1β is very central in the pathogenesis of devolving the septic symptoms in response to infection, and it may be a potential target for improving the survival of subgroups of septic patients.…”

Adipose tissue quantification and primary graft dysfunction after lung transplantation: The Lung Transplant Body Composition study

“…Alternately, greater IL-1RA may be a plasma marker of higher IL1-b production, as has been suggested in critical illness. 63 The further investigation of the role of adipose-mediated changes in IL1-RA production and IL1-b kinetics may identify a modifiable target for PGD prevention.…”

ARDS Subphenotypes: Understanding a Heterogeneous Syndrome

“…While these data certainly merits further investigation, translating biologic associations into effective treatments based on mechanism is by no means straightforward. For example, a retrospective analysis of a previous negative clinical trial of recombinant IL-1 receptor antagonist for sepsis found a treatment benefit in the subset of patients with higher levels of baseline IL-1 receptor antagonist, arguably a completely counterintuitive result [43].…”