Introduction

The pivotal role of immunity and inflammatory processes in epilepsy is increasingly recognized. To discuss the developments in this field, we convened a brain-storm meeting on Immunity and Inflammation in Epilepsy between basic science investigators and clinicians on September 16–18, 2010 at the Mario Negri Institute for Pharmacological Research, Milano, Italy (Fig. 1). The meeting was generously supported by the Commission on European Affairs of the International League Against Epilepsy (CEA-ILAE), the American Epilepsy Society (AES), and Agencia Italiana del Farmaco (AIFA). We are especially grateful to UCB Pharma, Basel, Switzerland; Sanofi-Aventis, Milano, Italy; and Questcor Union City, CA, U.S.A. for their support, which was instrumental for the realization of this meeting. The following articles summarize the major meeting outcomes by highlighting the state-of-art knowledge in this field, the emerging consensus on the type of epileptic disorders and syndromes in which immunity and inflammation may play an etiopathogenic role, the remaining challenges for future experimental and clinical research, and the therapeutic interventions envisaged for targeting immune/inflammatory mechanisms in epilepsy. Inflammation is defined as a homeostatic phenomenon induced by various types of tissue injuries, and consists of the rapid production of molecules with proinflammatory or antiinflammatory properties by cells of the immune system, including both innate and adaptive immunity cell types. Typically, this process is triggered to defend tissues against pathogen invasion during infections, but it can be also activated by endogenous ‘‘danger signals’’ released by threatened cells (Bianchi, 2007). In the brain, inflammation occurs as a result of activation of both resident parenchymal cells, such as microglia, astrocytes, and neurons constituting major players of innate immunity mechanisms, as well as via production of inflammatory mediators by leukocytes, which may penetrate the brain through the blood–brain barrier (these cell types include both components of peripheral innate immunity such as macrophages and granulocytes, and T and B cells as part of adaptive immunity). Several endogenous mechanisms have been identified to resolve inflammation after its first occurrence to prevent this phenomenon from becoming detrimental for tissue. When these regulatory mechanisms fail, inflammation may become chronic or last long enough to provoke tissue damage or dysfunction; therefore, a strict control of both the extent of inflammation and its permanence in tissue are considered important determinants of beneficial rather than pathologic outcomes. Long-lasting brain inflammation has been described after ischemic stroke, traumatic brain injury, or during chronic neurodegenerative diseases, and in all these conditions inflammation appears to contribute to the evolution of the pathology (Nguyen et al., 2002; Allan et al., 2005; Glass et al., 2010). In the last decade increasing research was directed to elucidate the possible role of immune and inflammatory processes in the etiopathogenesis of seizures in various types of epilepsy (Aarli, 2000; Palace & Lang, 2000; Choi et al., 2009; Vezzani et al., 2011). The first insights into the potential role of immunity and inflammation in human epilepsy raised from the evidence of anticonvulsant activity of adrenocorticotropic hormone (ACTH) and steroids in some infancy and childhood epilepsies (Low, 1958; Wirrell et al., 2005; Wheless et al., 2007). More recently, steroids have been administered in selected cases of refractory status epilepticus with variable efficacy (Bonati et al., 2006; Robakis & Hirsch, 2006; Shorvon et al., 2008; Kramer et al., 2009). Additional evidence came from febrile seizures and seizure aggravation upon infection (Dub et al., 2007), since both phenomena coincides with or are caused by increased proinflammatory molecules (Dinarello, 2004). Chronic and progressive brain inflammation was first identified in Rasmussen’s encephalitis, an epileptic syndrome associated with unilateral progressive destruction Address correspondence to Annamaria Vezzani, Department of Neuroscience, Laboratory of Experimental Neurology, Mario Negri Institute for Pharmacological Research, Via Giuseppe La Masa 19, I-20156 Milano, Italy. E-mail: vezzani@marionegri.it Stephan R egg, Division of Clinical Neurophysiology, Department of Neurology, University Hospital Basel, Petersgraben 4, CH-4031 Basel, Switzerland. E-mail: srueegg@uhbs.ch