Veränderungen von Leukoztenadhäsionsfaktoren und Toll-like Rezeptoren bei Patienten mit Epilepsie

Epilepsy is a disorder of the brain with a persistent tendency to suffer from seizures. Epileptic seizures are defined as excessive or synchronous neuronal activity which induces a transient occurrence of symptoms. There are many different aetiologies, which are merging partially. Inflammatory processes represent one category. Many links between the immune system and epilepsy are already known. An altered integrity of the blood-brain-barrier plays an important role. The detailed mechanisms however are not fully understood. With this study we aimed to gain further knowledge regarding immunological activities in patients with epilepsy. For that purpose, alterations of leucocyte adhesion factors and Toll-like receptors in peripheral blood of patients with epilepsy were investigated by using fluorescence activated cell sorting, interictally as well as in context with seizures. Seizure type, hippocampal sclerosis and side of seizure onset in the brain were considered as influencing factors. We included 35 patients from the video-electroencephalography monitoring unit and the epilepsy outpatient department of the Philipps-University Marburg who were diagnosed with focal epilepsy. Blood samples were taken at admission day (Baseline), immediately postictally, 1 hour postictally and 24 hours postictally, if possible. The interictal samples were compared to 20 healthy controls. The main findings show postictal increase of intercellular adhesion molecule-1 positive cytotoxic cells (CD54+/CD56+ and CD54+/CD8+) and Toll-like receptor-4 positive monocytes (CD284+/CD14+), as well as postictal decrease of intercellular adhesion molecule-1 positive T helper cells (CD54+/CD4+). In comparison with healthy controls, we noticed a higher rate of intercellular adhesion molecule-1 positive cytotoxic T cells (CD54+/CD8+) interictally. The course was partially dependent of seizure type, aetiology and side of seizure onset. The postictal increase of natural killer cells and cytotoxic T cells has been described in former and in recent studies. Also, the decrease of T helper cells was shown in previous studies. Higher rates of Toll-like receptor-4 carrying cells in patients with epilepsy were noticed also in other studies. In animal models inhibitors of intercellular adhesion molecule-1 and Toll-like receptor-4 indicated a seizure suppressing effect. With our study we can support these findings and provide a better understanding of the immunological mechanisms in epileptic seizures. This might contribute to the development of new seizure suppressing drugs in the future. Taken together, the findings of this study and former studies suggest that with their influence on the blood-brain-barrier both, intercellular adhesion molecule-1 and Toll-like receptor-4 play an important role in ictogenesis. To give a more detailed statement and to better understand the reciprocal effects of seizures, stress and alterations of the blood-brain-barrier, more precise studies with more frequent blood samples and a larger number of patients would be needed.