IL-17A monoclonal antibody as a translational therapy for post-cardiac arrest brain injury: clinical and preclinical evidence.

Abstract

Post-cardiac arrest brain injury (PCABI) is a major cause of mortality and disability among cardiac arrest (CA) survivors. The role of interleukin-17A (IL-17A) as a prognostic biomarker and therapeutic target in PCABI remains unvalidated. Eighty adult CA patients with return of spontaneous circulation (ROSC) and 10 controls were enrolled. Serum IL-17A was measured at 24 h post-ROSC. Thirty-day neurological outcomes were classified by the Cerebral Performance Category (CPC) scale. The prognostic value of IL-17A was evaluated using multivariable logistic regression and ROC curves. In rats asphyxial CA model, animals received vehicle or anti-IL-17A monoclonal antibody (secukinumab). Neurological function, survival, and biomarkers were assessed. Serum IL-17A levels were significantly higher in CA patients than in controls (2.42 ± 1.25 vs. 0.63 ± 0.34 pg/mL, p < 0.001). Patients with poor neurological outcomes (CPC 3-5) had higher IL-17A levels (2.72 ± 1.25 vs. 1.91 ± 1.10 pg/mL, p = 0.023). IL-17A independently predicted poor neurological outcomes (adjusted OR = 3.56, 95 % CI = 1.31-9.63). ROC analysis showed an AUC of 0.702 for predicting neurological dysfunction. In the rat model, anti-IL-17A mAb treatment significantly increased 11-day survival (62.5 % vs. 30.3 %), improved neurological scores, and enhanced performance in the Morris water maze test. Mechanistically, anti-IL-17A mAb treatment reduced the levels of TNF-α, NSE, and NfL in serum and brain tissues. Elevated serum IL-17A is a potential early predictor of poor outcomes in PCABI. Early administration of anti-IL-17A mAb improved neurological recovery and survival in the experimental CA model by attenuating neuroinflammation.