Introduction: The impact of the inflammatory response after intracerebral hemorrhage (ICH) has not been well characterized in patients and little is known about the relationship between early markers of inflammation and functional outcome. It is hypothesized that cytokine levels may be associated with three-month functional outcome and radiologic markers of secondary injury.
Methods: Fifty-four patients with spontaneous ICH were prospectively enrolled at Yale-New Haven Hospital. Blood samples were collected at 24 (n=44) and 72 (n = 33) hours post-ICH. Plasma cytokine levels were measured using commercially available multiplex ELISA kits (Millipore). Modified Rankin Scale (mRS) was collected at three months by telephone interview. Associations between cytokines and outcome were assessed using ordinal logistics regression. Linear regression was used to evaluate the association between cytokine levels and markers of secondary injury.
Results: IL-6 was correlated with ICH volume (p = 0.003) and PHE volume (p = 0.009) in univariable analysis. In multivariable analysis, IL-6 was associated with midline shift after adjustment for ICH volume (p=0.027). 24h IL-6 (p < 0.001), IL-10 (p < 0.001), IL-15 (p = 0.001), admission Glasgow Coma Score (GCS), ICH volume, ICH Score, and external ventricular drain (EVD) placement were associated with higher (worse) mRS in univariable ordinal regression. After adjustment for the ICH score, 24h IL-6 (OR 2.00, 95% CI 1.2-3.3, p = 0.003) and IL-15 (OR 2.7, 95% CI 1.4-5.0, p = 0.007) were significantly associated with worse mRS.
Conclusions: Plasma IL-6 is independently associated with 24h midline shift, a measure of global hemispheric swelling, and with functional outcome after spontaneous ICH. These data are consistent with the early robust increase in brain IL-6 in experimental models of ICH. These data warrant further investigation of IL-6 levels as a biomarker for secondary injury and poor outcome in ICH.