Ventura A C, Böhnke M
Augen- und Poliklinik des Inselspitals, Universität Bern, CH-3010 Bern, Switzerland.
Br J Ophthalmol. 2001 Sep;85(9):1110-4. doi: 10.1136/bjo.85.9.1110.
BACKGROUND/AIMS: Scientific interest in pentoxifylline has been reawakened owing to the recognised effects of this drug on immune functions, particularly its influence on cytokine production. In a previous study, the authors demonstrated that spiking of organ culture media with endotoxin elicited a marked enhancement in the release of IL-6 and IL-8 from corneal tissue and that these events coincided with degenerative changes in endothelial cells and a higher incidence of actual loss among this population. Since traces of donor derived endotoxin can be detected in up to 50% of corneal organ cultures, this substance may have a direct influence on graft viability or trigger inflammatory responses in the host. They, therefore, wished to ascertain whether supplementation of media with pentoxifylline improved endothelial cell survival in organ cultured donor corneas.
12 fellow pairs of donor corneas were cultured for 20 days, with a change of medium on day 10: One of each pair was incubated in the absence, and the other in the presence, of pentoxifylline (25 microg/ml). Samples of medium were withdrawn at regular intervals during the course of incubation and screened for cytokines IL-6, IL-8, and prostaglandin E2 by ELISA. Endothelial cell morphology and numerical density were assessed on days 0, 10 and 20.
Addition of pentoxifylline to organ culture media led to a significant improvement in endothelial cell survival. This drug also elicited a significant increase in the level of IL-6 and marginally suppressed that of IL-8 during the initial 10 day phase of incubation. During the second 10-20 day phase, the level of both IL-6 and IL-8 decreased significantly in the presence of pentoxifylline, the relation between these two cytokines being the inverse of that observed in the absence of the drug. No significant changes in the level of prostaglandin E2 were apparent.
The addition of pentoxifylline to organ culture media leads, ultimately, to a suppression of IL-6 and IL-8 secretion by corneal tissue. The potentially damaging effects of these cytokines are thereby quelled, as evidenced by the improvement in endothelial cell survival.
背景/目的：己酮可可碱对免疫功能的公认作用，尤其是其对细胞因子产生的影响，重新唤起了科学界对它的兴趣。在先前的一项研究中，作者证明向内毒素添加到器官培养基中会显著增强角膜组织中IL-6和IL-8的释放，并且这些事件与内皮细胞的退行性变化以及该群体中实际损失的更高发生率相吻合。由于在高达50%的角膜器官培养物中可以检测到供体来源的内毒素痕迹，这种物质可能对移植物的活力有直接影响或触发宿主中的炎症反应。因此，他们希望确定在培养基中添加己酮可可碱是否能提高器官培养的供体角膜中内皮细胞的存活率。
12对供体角膜进行培养20天，在第10天更换培养基：每对中的一个在无己酮可可碱（25微克/毫升）的情况下孵育，另一个在有己酮可可碱的情况下孵育。在孵育过程中定期取出培养基样本，并通过ELISA检测细胞因子IL-6、IL-8和前列腺素E2。在第0、10和20天评估内皮细胞形态和数量密度。
向器官培养基中添加己酮可可碱可显著提高内皮细胞的存活率。在孵育的最初10天阶段，这种药物还使IL-6水平显著增加，并略微抑制了IL-8的水平。在第二个10 - 20天阶段，在有己酮可可碱的情况下，IL-6和IL-8的水平均显著下降，这两种细胞因子之间的关系与在无药物情况下观察到的相反。前列腺素E2水平没有明显变化。
向器官培养基中添加己酮可可碱最终会抑制角膜组织中IL-6和IL-8的分泌。这些细胞因子的潜在破坏作用因此得到抑制，内皮细胞存活率的提高证明了这一点。
