Association of Serum IL-6 (Interleukin 6) With Functional Outcome After Intracerebral Hemorrhage

Stroke. 2021 May;52(5):1733-1740. doi: 10.1161/STROKEAHA.120.032888. Epub 2021 Mar 8.


Background and objectives: IL-6 (interleukin 6) is a proinflammatory cytokine and an established biomarker in acute brain injury. We sought to determine whether admission IL-6 levels are associated with severity and functional outcome after spontaneous intracerebral hemorrhage (ICH).

Methods: We performed an exploratory analysis of the recombinant activated FAST trial (Factor VII for Acute ICH). Patients with admission serum IL-6 levels were included. Regression analyses were used to assess the associations between IL-6 and 90-day modified Rankin Scale. In secondary analyses, we used linear regression to evaluate the association between IL-6 and baseline ICH and perihematomal edema volumes.

Results: Of 841 enrolled patients, we included 552 (66%) with available admission IL-6 levels (mean age 64 [SD 13], female sex 203 [37%]). IL-6 was associated with poor outcome (modified Rankin Scale, 4-6; per additional 1 ng/L, odds ratio, 1.30 [95% CI, 1.04-1.63]; P=0.02) after adjustment for known predictors of outcome after ICH and treatment group. IL-6 was associated with ICH volume after adjustment for age, sex, and ICH location, and this association was modified by location (multivariable interaction, P=0.002), with a stronger association seen in lobar (β, 12.51 [95% CI, 6.47-18.55], P<0.001) versus nonlobar (β 5.32 [95% CI, 3.36-7.28], P<0.001) location. IL-6 was associated with perihematomal edema volume after adjustment for age, sex, ICH volume, and ICH location (β 1.22 [95% CI, 0.15-2.29], P=0.03). Treatment group was not associated with IL-6 levels or outcome.

Conclusions: In the FAST trial population, higher admission IL-6 levels were associated with worse 90-day functional outcome and larger ICH and perihematomal edema volumes.

Keywords: brain injury; cerebral hemorrhage; cytokine; edema; odds ratio.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Brain Edema* / blood
  • Brain Edema* / drug therapy
  • Brain Edema* / etiology
  • Brain Edema* / pathology
  • Cerebral Hemorrhage* / blood
  • Cerebral Hemorrhage* / complications
  • Cerebral Hemorrhage* / drug therapy
  • Cerebral Hemorrhage* / pathology
  • Double-Blind Method
  • Factor VIIa / administration & dosage*
  • Female
  • Humans
  • Interleukin-6 / blood*
  • Male
  • Middle Aged
  • Patient Acuity*
  • Recombinant Proteins / administration & dosage


  • IL6 protein, human
  • Interleukin-6
  • Recombinant Proteins
  • recombinant FVIIa
  • Factor VIIa