Pentoxifylline influences the autocrine function of organ cultured donor corneas and enhances endothelial cell survival

Background/aims-Scientific interest in pentoxifylline has been reawakened o wing to the recognised effects of this drug on immune functions, particular ly its influence on cytokine production. In a previous study, the authors d emonstrated that spiking of organ culture media with endotoxin elicited a m arked enhancement in the release of IL-6 and IL-8 from corneal tissue and t hat these events coincided with degenerative changes in endothelial cells a nd 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 cult ures, this substance may have a direct influence on graft viability or trig ger inflammatory responses in the host. They, therefore, wished to ascertai n whether supplementation of media with pentoxifylline improved endothelial cell survival in organ cultured donor corneas. Methods-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 mug/ml). Samples of me dium were withdrawn at regular intervals during the course of incubation an d screened for cytokines IL-6, IL-8, and prostaglandin E2 by ELISA. Endothe lial cell morphology and numerical density were assessed on days 0, 10 and 20. Results-Addition of pentoxifylline to organ culture media led to a signific ant improvement in endothelial cell survival. This drug also elicited a sig nificant 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 d ay phase, the level of both IL-6 and IL-8 decreased significantly in the pr esence of pentoxifylline, the relation between these two cytokines being th e inverse of that observed in the absence of the drug. No significant chang es in the level of prostaglandin E2 were apparent. of Conclusion-The addition of pentoxifylline to organ culture media leads, ult imately, to a suppression of IL-6 and IL-8 secretion by corneal tissue. The potentially damaging effects of these cytokines are thereby quelled, as ev idenced by the improvement in endothelial cell survival.