Abstract Body: Background: Stroke outcomes vary with ethnicity, with immune response markers like interferon-gamma (IFN-γ) playing a significant role in stroke pathophysiology. IFN-γ, a proinflammatory cytokine produced by T cells and natural killer (NK) cells, regulates immune responses by activating macrophages and promoting inflammation. Baseline IFN-γ levels in healthy African Americans are similar to Whites. Ethnic variations in IFN-γ have been noted in diseases like Rheumatoid arthritis and Hepatitis C. Given the worse stroke outcomes experienced by African Americans, we hypothesized that IFN-γ levels may vary with sex and ethnicity post stroke.
Methods: Plasma samples were collected from stroke patients admitted to Memorial Hermann Hospital, Houston by UTHealth biobank within 24 hours of admission and analyzed for IFN-γ levels using ELISA. Patients were stratified by sex and ethnicity (Black, Hispanic, White), and statistical analysis was performed using ANOVA, with post-hoc pairwise comparisons. Multilinear regression analysis was conducted to examine the adjusted associations.
Results: The mean age of patients was 63.6 years, 35% were women, 88% had hypertension, 47% had diabetes mellitus, and 53% had hyperlipidemia. In men, no significant differences in plasma IFN-γ levels were observed across ethnic groups. However, in women (n=21), IFN-γ levels varied significantly by ethnicity, p=0.04. African American women had the highest IFN-γ levels, 4.0±1.7 pg/mL, followed by Hispanic 2.6±1.6 pg/mL, and White women 1.5±0.8 pg/mL. Pairwise comparisons showed a significant difference between African American and White women (p=0.04), but no difference between Hispanic and White women, p=0.62. This association held true when adjusted for other co-morbidities in the multilinear model.
Conclusions: The higher IFN-γ levels observed in African American women likely reflects an exaggerated proinflammatory response to stroke in women. This heightened response may contribute to worse stroke outcomes in this population. The absence of such differences in men suggests a potential sex-specific inflammatory response to stroke. Understanding the up and downstream pathways of IFN-γ in African American women after ischemic stroke can help elucidate the mechanisms behind disparities in stroke and explore potential sex and ethnicity specific therapeutic interventions targeting inflammation.