Expression of inflammatory cytokines in CADASIL and their associations with clinical and neuroimaging features

Li Bai¹Haotian Yan¹Zhongao Wang¹Qing Peng¹Haiqiang Jin¹Yun Chuang Sun¹LI Fan¹Wei Zhang¹Zihao Zhang²Zhaoxia Wang¹Yun Yuan¹Hongjun Hao¹Tao Wu¹Chen Ling^1*

• ¹Peking University First Hospital, Beijing, China
• ²University of the Chinese Academy of Sciences, Beijing, China

The aim of our study is to explore the expression levels of inflammatory cytokines in patients with CADASIL, to assess the correlation between inflammatory cytokines and clinical/MRI features of the patients. We recruited 54 patients with CADASIL and 28 healthy controls and detected the expression levels of the following inflammatory cytokines in peripheral blood: interferon (IFN)-γ, tumor necrosis factor (TNF)-α, TNF-β, interleukin (IL)-1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-17F, and IL-22. We analyzed the relationship between the expression levels of the inflammatory cytokines and the clinical/MRI features. The expression of most inflammatory cytokines were significantly higher in CADASIL patients , including IFN-γ (z = −5.335, P < 0.001), TNF-α (z = −4.880, P < 0.001), TNF-β (z = −2.401, P = 0.019), IL-1β ( z = -2.831, P = 0.007), IL-4 ( z = −4.039, P < 0.001), IL-5 (z = −4.523, P < 0.001), IL-6 (z = −3.545, P < 0.001), IL-8 (z = −5.667, P < 0.001), IL-17F (z = −3.986, P < 0.001) and IL-22 (z = −5.325, P < 0.001). The increased expression level of TNF-β was correlated with abnormal mRS scores in patients with CADASIL (odds ratio [OR] = 6.147, 95% CI: 1.324-28.535; P = 0.020) after adjustment for age, sex, history of hypertension and diabetes. The expression level of TNF-β was also associated with MMSE (β = -0.281, 95% CI:-5.325--0.866, P = 0.008) and apathy scores (β = 0.388, 95% CI:2.554-16.328, P = 0.008) after adjusting for age, sex, educational years, history of hypertension and diabetes. There was a positive correlation between the expression level of TNF-β and the number of CMBs in deep ( β = 0.314, 95% CI:2.989-39.461, P = 0.023) and lobar region ( β = 0.433, 95% CI:15.363-59.857, P = 0.001) after adjusting for age, sex, history of hypertension and diabetes. Our results indicate that diffuse inflammatory pathway activation occurs in CADASIL. The increased expression level of TNF-β was associated with higher CMBs burden and poor clinical scores. Our findings suggest that the inflammatory pathway, particularly the TNF-related inflammatory pathway, may be involved in the disease progression of CADASIL.