INTERLEUKIN-6 AND DEVELOPMENT OF VASOSPASM AFTER SUBARACHNOID HEMORRHAGE

The authors characterized the role of interleukins in the cerebrospina l fluid (CSF) in the development of vasospasm after subarachnoid haemo rrhage (SAH), particularly interleukin-6 (IL-6). Concentrations of int erleukin-1 beta (IL-1 beta), IL-6, and interleukin-8 (IL-8) were measu red serially in CSF of 24 patients and in serum of 9 patients with SAH and correlated clinically. Additionally, the effects of the same cyto kines on the cerebral arteries of dogs were analyzed on angiograms aft er intracisternal injection. Changes in levels of eicosanoids, angioge nic factors, and soluble cell adhesion molecules were investigated in the CSF of injected dogs. CSF concentrations of IL-6 and IL-8 were ele vated significantly above control levels from the acute stage of SAH u ntil the chronic stage. Patients with symptomatic vasospasm had signif icantly higher levels of IL-6 as well as IL-8 in CSF on days 5 and 7. Intracisternal injection of IL-6 induced long-lasting vasoconstriction in five out of eight dogs, while IL-8 did not. The diameter of canine basilar artery after IL-6 was reduced 29 +/- 5% from pretreatment dia meter at 8 hours. Prostaglandins E-2 and I-2 were elevated in CSF for the first 4.5 hour of this IL-6-induced vasospasm. Neither angioenic f actors such as platelet-derived growth factor-AB and vascular endothel ial growth factor nor soluble cell adhesion molecules were significant ly elevated in CSF. IL-6, which increases to very high concentrations in CSF after SAH, may be important in inducing vasospasm, as IL-6 prod uced long-lasting vasoconstriction in the canine cerebral artery, whic h may be partly related to activation of the prostaglandin cascade.