The screening assessment of pro-inflammatory, anti-inflammatory, Th1, Th2 and Th17 cytokines in saliva of patients with ischemic stroke.

Introduction: Ischemic stroke leads to hypoxia of brain structures, causes inflammation and tissue necrosis. Since the blood-brain barrier is damaged, inflammatory mediators can enter the bloodstream and saliva. This case-control study examines pro-inflammatory, anti-inflammatory, Th1, and Th2 cytokines in the unstimulated saliva of stroke patients and explores the association between these biomarkers and clinical status. Patients and methods: The study group included 22 patients with ischemic stroke, while the control group included 22 healthy individuals that were matched for age, sex, dental, periodontal and oral hygiene status to the study group. Unstimulated saliva was collected from each patient. In each sample, the inflammatory profile was determined using the multiplex ELISA method. Due to the lack of normal distribution, the Mann-Whitney U test was used for comparisons. The research was approved by the Bioethics Committee of the Poznan University of Medical Sciences (59/19, 890/19, 504/21). Results: In the unstimulated saliva of stroke patients, significantly higher levels of pro-inflammatory cytokines (IL-1β (p=0.0003), TNF-α (p≤0.0001), TNF-β; (p≤0.0001)), anti-inflammatory cytokines (IL-1ra (p≤0.0001), TRAIL (p=0.0206)), Th1 cytokines (IFN-γ (p≤0.0001), IL-2Rα (p=0.0021) and IL-12 (p40) (p≤0.0001)) and Th2 cytokines (IL-6 (p=0.0023)) were found compared to healthy participants. Interestingly, Addenbrooke's Cognitive Examination Revised (ACE-R) correlated negatively with TNF-α (p=0.01, r=-0.53), TNF-β (p=0.02, r=-0.60) and IFN-γ (p=0.02, r=-0.50). The Functional Independence Measure (FIM) exhibited a positive association with IL-6 (p=0.003, r=0.62) and BI (p=0.001, r=0.66). The positive correlation was found between Sitting Balance Scale (SBS) and IL-6 (p=0.02, r=0.52). Conclusions: Stroke patients exhibit altered salivary composition characterized by increased secretion of inflammatory mediators. The obtained results do not indicate the dominance of any of the branches of the immune response. The concentration of salivary TNF-α, TNF-β, IFN-γ and IL-12 significantly distinguish patients with ischemic stroke from healthy individuals. Although validation of the results in a larger patient population is necessary, salivary cytokines show potential as diagnostic biomarkers.