Intractable Epilepsy (IE) and Responses to Anakinra, a Human Recombinant IL-1 Receptor Agonist (IL-1ra): Case Reports

Abstract

Patients with intractable seizures (IE) who failed to respond currently available treatment measures are clinically challenging, causing significant morbidity and even mortality. Better understanding of contributing factors for IE will be helpful for exploring additional treatment options. A role of inflammation has long been suspected in pathogenesis of epilepsy, especially in idiopathic epilepsy with diffuse epileptic activity. In rodent models of epilepsy, blockage of inflammatory mediators such as interleukin 1-β (IL-1β) and IL-6 attenuates epileptic activities. However, therapeutic effects of blockers of such inflammatory mediators have not been addressed in patients with IE.This manuscript reports 4 IE cases in which anakira, a human recombinant IL-1 receptor antagonist (IL-1ra), was clinically effective in controlling their epileptic activity in a dose-dependent manner. In these patients, we also observed changes in ratios of IL-1β/IL-10 produced by peripheral blood monocytes, surrogates of bone marrow derived microglial cells. These findings could be associated with seizure control status.These presented cases indicate a possible therapeutic use of a commercially available IL-1β blocker (anakinra) and therapeutic utility of the IL-1β/IL-10 ratios produced by peripheral blood monocytes for assessing responses to this immune-modulating agent.