FAILURE OF FK-506, A NEW IMMUNOSUPPRESSANT, TO PREVENT CEREBRAL VASOSPASM IN A CANINE 2-HEMORRHAGE MODEL

In order to clarify the possible role of immunological reaction in the pathogenesis of cerebral vasospasm, the authors examined the prophyla ctic effect of the immunosuppressant agents FK-506 and cyclosporin A o n chronic vasospasm in a canine two-hemorrhage model. While a mean con striction of the basilar artery to 81.0% +/- 4.0% (+/- standard error of the mean) occurred on Day 2 and to 63.8% +/- 3.5% on Day 7 in the u ntreated group, constriction to 77.9% +/- 3.4% on Day 2 and 62.8% +/- 3.0% on Day 7 was demonstrated in the FK-506-treated group (difference not significant). This tendency was also noted in the cyclosporin A-t reated group, with basilar artery constriction to 81.8% +/- 3.7% and 5 6.3% +/- 2.7%, respectively (difference not significant). The histolog ical changes of the basilar artery, including corrugation of the elast ic lamina, detachment of endothelial cells, and vacuolar formation in the smooth-muscle layer were not different in the two treated groups a nd the one control group. Since these immunosuppressant agents are kno wn to inhibit the release of interleukin-2 (IL-2), the level of IL-2 w as examined in the cerebrospinal fluid of patients with cerebral vasos pasm. While interleukin-1 gradually increased in level as time passed, the level of IL-2 was consistently low during the course of the study , indicating less participation of IL-2 in the pathogenesis of cerebra l vasospasm. This clinical observation matched the experimental result s. The authors conclude that cell-mediated immunoreaction, initiated m ainly by IL-2, plays little role in the pathogenesis of cerebral vasos pasm.