Vitaliti Giovanna, Pavone Piero, Mahmood Fahad, Nunnari Giuseppe, Falsaperla Raffaele
Department of Paediatrics and Pediatric Acute and Emergency Unit; Policlinico-Vittorio Emanuele University Hospital; University of Catania; Catania, Italy.
University London College Medical School; University of London; London, UK.
Hum Vaccin Immunother. 2014;10(4):868-75. doi: 10.4161/hv.28400. Epub 2014 Mar 7.
An increasing body of literature data suggests that inflammation, and in particular neuroinflammation, is involved in the pathophysiology of particular forms of epilepsy and convulsive disorders. Animal models have been used to identify inflammatory triggers in epileptogenesis and inflammation has recently been shown to enhance seizures. For example, pharmacological blockade of the IL-1beta/IL-1 receptor type 1 axis during epileptogenesis has been demonstrated to provide neuroprotection in temporal lobe epilepsy. Furthermore, experimental models have suggested that neural damage and the onset of spontaneous recurrent seizures are modulated via complex interactions between innate and adaptive immunity. However, it has also been suggested that inflammation can occur as a result of epilepsy, since animal models have also shown that seizure activity can induce neuroinflammation, and that recurrent seizures maintain chronic inflammation, thereby perpetuating seizures. On the basis of these observations, it has been suggested that immune-mediated therapeutic strategies may be beneficial for treating some drug resistant epilepsies with an underlying demonstrable inflammatory process. Although the potential mechanisms of immunotherapeutic strategies in drug-resistant seizures have been extensively discussed, evidence on the efficacy of such therapy is limited. However, recent research efforts have been directed toward utilizing the potential therapeutic benefits of anti-inflammatory agents in neurological disease and these are now considered prime candidates in the ongoing search for novel anti-epileptic drugs. The objective of our review is to highlight the immunological features of the pathogenesis of seizures and to analyze possible immunotherapeutic approaches for drug resistant epilepsies that can alter the immune-mediated pathogenesis.
越来越多的文献数据表明，炎症，尤其是神经炎症，参与了特定形式的癫痫和惊厥性疾病的病理生理过程。动物模型已被用于确定癫痫发生过程中的炎症触发因素，并且最近已证明炎症会增强癫痫发作。例如，在癫痫发生过程中对白细胞介素-1β/白细胞介素-1受体1型轴进行药理学阻断已被证明可在颞叶癫痫中提供神经保护作用。此外，实验模型表明，神经损伤和自发性反复癫痫发作的发生是通过先天免疫和适应性免疫之间的复杂相互作用来调节的。然而，也有人提出炎症可能是癫痫的结果，因为动物模型还表明癫痫发作活动可诱导神经炎症，并且反复癫痫发作会维持慢性炎症，从而使癫痫持续存在。基于这些观察结果，有人提出免疫介导的治疗策略可能有助于治疗一些具有潜在明显炎症过程的耐药性癫痫。尽管免疫治疗策略在耐药性癫痫发作中的潜在机制已被广泛讨论，但关于这种治疗效果的证据有限。然而，最近的研究工作一直致力于利用抗炎药物在神经系统疾病中的潜在治疗益处，这些药物现在被认为是正在进行的新型抗癫痫药物研究中的主要候选药物。我们综述的目的是强调癫痫发病机制的免疫学特征，并分析针对耐药性癫痫的可能免疫治疗方法，这些方法可以改变免疫介导的发病机制。
