Legacy Health System, Portland, Oregon, USA.
J Biomed Mater Res A. 2010 Jul;94(1):280-7. doi: 10.1002/jbm.a.32651.
Chronically implanted biosensors typically lose sensitivity 1-2 months after implantation, due in large part to the development of a collagen-rich capsule that prevents analytes of interest from reaching the biosensor. Corticosteroids are likely candidates for reducing collagen deposition but these compounds have many serious side effects when given over a prolonged period. One method of assessing whether or not locally released corticosteroids have a systemic effect is to measure cortisol concentrations in venous serum. We hypothesized that a very low release rate of the potent corticosteroid, dexamethasone, would lead to a localized anti-inflammatory effect without systemic effects. We found that reduction in subcutaneous granulocytes (primarily eosinophils), and to a lesser extent, reduction of macrophages served as a good local indicator of the steroid effect. When released over a 28-day period, a total dexamethasone dose of < or =0.1 mg/kg led to a consistent reduction in the number of granulocytes and macrophages found in the local vicinity of the implant without a reduction of these cells at distant tissue locations. The lack of suppression of serum cortisol with these doses confirmed that low-release rates of dexamethasone can lead to consistent local anti-inflammatory effects without distant, systemic effects. (c) 2010 Wiley Periodicals, Inc. J Biomed Mater Res, 2010.
慢性植入生物传感器通常在植入后 1-2 个月失去敏感性，这在很大程度上是由于形成富含胶原蛋白的囊，阻止了感兴趣的分析物到达生物传感器。皮质类固醇可能是减少胶原蛋白沉积的候选物，但这些化合物在长期使用时会产生许多严重的副作用。评估局部释放皮质类固醇是否具有全身作用的一种方法是测量静脉血清中的皮质醇浓度。我们假设，强力皮质类固醇地塞米松的极低释放率将导致局部抗炎作用而没有全身作用。我们发现，皮下粒细胞（主要是嗜酸性粒细胞）的减少，以及在较小程度上巨噬细胞的减少，可作为类固醇作用的良好局部指标。当在 28 天的时间内释放时，总地塞米松剂量<或=0.1mg/kg 导致植入物附近的粒细胞和巨噬细胞数量持续减少，而在远离组织部位的这些细胞没有减少。这些剂量对地塞米松血清皮质醇的抑制作用缺乏证实了低释放率的地塞米松可以导致一致的局部抗炎作用而没有远处的全身作用。（c）2010 年 Wiley 期刊，Inc. J Biomed Mater Res，2010。
