Introduction: The objective of this study was to evaluate the effect of therapeutic moderate hypothermia (MH, Tcore33-34°C) compared to normothermia (NT, Tcore36.5-37°C) on innate immune responses and functional outcome.
Methods: In a clinical trial of temperature modulation after ICH, we measured daily levels of cytokine/chemokine TNFα, IL1, IL6 (M1 response), IL10 (M2 response), and CCL2 in peripheral blood of enrolled patients from day (D) 1-7. Levels were log-transformed to meet assumptions of normality. We used mixed models to evaluate the effect of temperature on the expression of cytokine levels, the t-test to determine the association between cumulative CCL2 log-levels and functional outcome, and Cox-regression to determine the impact of MH on long-term functional outcome adjusted for ICH score (median>2), and initial Sequential Organ Failure Assessment Score (iSOFA, median>3). Poor outcome was defined as mRS=5-6.
Results: 10 ICH patients participated in the study (MH=5, NT=5). Median age was 57 years (IQR 22), 55% women, 66% were Black, median GCS was 7 (IQR 4), and median ICH score was 2 (IQR 1). TNFα, IL1, IL6 vs. IL10 log-ratios decreased significantly over time in MH (Fig.1). Mixed models revealed a significant interaction (arm*day) for MH compared to NT for TNFα (β=-0.1, p=.008), IL1 (β=-.01, p=.02), and IL6 (β=-.04, p=.04) (Fig.1). Cumulative CCL2 log-levels at D7 were lower in ICH patients with mRS 0-4 at 6 months as compared to mRS 5-6 (3.7 ± 0.1 Log-pg/mL vs. 4.2 ± 0.1 Log-pg/mL, p=0.02). Adjusting for ICH score (HR 4.0, 95%CI 0.34-97) and iSOFA (HR 8.8, 95%CI 0.9-295), MH was not associated with poor outcome (HR 0.8, 95%CI 0.5-8.9).
Conclusions: This novel data suggest that MH significantly up-regulates the anti-inflammatory M2 response compared to NT after ICH. Higher cumulative log-levels of CCL2 are associated with long-term poor functional outcome. MH was not associated with worst functional outcome.