Ischemic Stroke: A Case Study

Introduction
In the last few years efforts has been made to better understand the pathophysiology of stroke, especially ischemic stroke that is responsible for 80 percent of the cases. It has been stablished that the immune system, and specifically the inflammatory compounds, play an important role in the development and aggravation of ischemic stroke. The different ways that an inflammatory environment can contribute to the stroke development are: alteration in the vascular reactivity or vasculitis, thus promoting vasculopathy; thrombosis and atherosclerosis (ref 11, 15, 18-22 macrez).
Even though there are various types of immune cells (macrophages, monocytes and T cells, etc) contributing to the development of stroke the focus of this review

Recently iIt has been stablished that inflammatory mediators have importance in neuronal damaged caused by ischemic stroke (Loddick [minami, relton, yamaski] and IL-1 has been related it as one of the most important cytokines that participates in ischemic brain injury (Loddick [minami, Yamasaki]. One of the clinical strategies that has been developed to minimize the IL-1 neuronal damage is the administration of Interleukin-1 receptor antagonist (IL-1ra). Animal models has shown that ÌL-1ra is responsible to block all actions of IL-1 and to reduce the damages caused by brain trauma, cerebral ischemia and neurotoxin infusions (rothwell).
In this clinical trial (emsley) from 218 patients screened just 34 were randomized and allocated in two groups: placebo or treatment group. The group treated has received 100 mg as a loading dose of IL1-ra intravenously followed by administrations of 2mg/kg/h over 72h (del zoppo). After the treatment the patients were assessed after 7 days and 3 months. The primary hypothesis tested in this trial was if IL-1ra is safe, measuring the Severe Adverse Effects (SAE) and the second hypothesis was to analyze its efficacy. The authors have pointed that no SAE was registered as consequence of the

The efficacy of Il-1ra was assessed

The authors have stated that the choice of dose regimen as 100 mg bolus followed by 2 mg/kg/h infusion for 72 hours was made based on a previous study (opal) considering the highest dose tolerated. The study cited evaluated the effects of IL-1ra in a severe sepsis mode which can represent results considerably different when compared to an ischemic stroke model. The best option would be to perform dose-response assays to determine the best dose regimen for this model.
This clinical trial has presented promising results related to safety and efficacy of Il-1ra in an ischemic stroke model, being an important step to the development of IL-1ra as a potential drug. However, it fails in some important points such as the design of the trial, once the number of patients should be higher to give a better statistical significance and the dose regimen should had been performed with dose-response assays. Furthermore, as del zoppo indicates, there are some failures to translate the findings from animal models to human studies, as well as some lack of understanding of immunology