K. Nagata et al., FAILURE OF FK-506, A NEW IMMUNOSUPPRESSANT, TO PREVENT CEREBRAL VASOSPASM IN A CANINE 2-HEMORRHAGE MODEL, Journal of neurosurgery, 79(5), 1993, pp. 710-715
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.