Interleukin-6 and Development of Vasospasm after Subarachnoid Haemorrhage

Abstract

The authors characterized the role of interleukins in the cerebrospinal fluid (CSF) in the development of vasospasm after subarachnoid haemorrhage (SAH), particularly interleukin-6 (IL-6). Concentrations of interleukin-1 beta (IL-1 beta), IL-6, and interleukin-8 (IL-8) were measured serially in CSF of 24 patients and in serum of 9 patients with SAH and correlated clinically. Additionally, the effects of the same cytokines on the cerebral arteries of dogs were analyzed on angiograms after intracisternal injection. Changes in levels of eicosanoids, angiogenic factors, and soluble cell adhesion molecules were investigated in the CSF of injected dogs. CSF concentrations of IL-6 and IL-8 were elevated significantly above control levels from the acute stage of SAH until the chronic stage. Patients with symptomatic vasospasm had significantly 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 diameter at 8 hours. Prostaglandins E2 and I2 were elevated in CSF for the first 4.5 hour of this IL-6-induced vasospasm. Neither angiogenic factors such as platelet-derived growth factor-AB and vascular endothelial growth factor nor soluble cell adhesion molecules were significantly elevated in CSF. IL-6, which increases to very high concentrations in CSF after SAH, may be important in inducing vasospasm, as IL-6 produced long-lasting vasoconstriction in the canine cerebral artery, which may be partly related to activation of the prostaglandin cascade.

Systemic interleukin-6 concentrations in patients with perimesencephalic non-aneurysmal subarachnoid hemorrhage

“…[8][9][10] In particular high levels of IL-6, a pleioptropic proinflammatory cytokine, in the CSF have been linked with the occurrence of CVS and outcome. [10][11][12][13] Systemic IL-6 has been shown to be an independent predictor of outcome in unselected critically ill patients. 25 Less has been reported on systemic IL-6 levels in patients with aSAH.…”

“…[8][9][10] Higher levels of interleukin (IL)-6 in the cerebro-spinal fluid (CSF) have been linked to the occurrence of CVS and worse outcome. [10][11][12][13] Further, the occurrence of systemic inflammatory response syndrome has been linked to the development of CVS and worse outcome in patients with aSAH. 14,15 The possible significance of systemic leukocyte count has been discussed earlier.…”

“…16,17 Less has been reported on systemic IL-6 levels, however, increased levels were described. 11,18,19 Systemic IL-6 might originate from the central nervous system and/or reflect the systemic inflammatory response. The systemic IL-6 levels can be assumed to reflect the severity of illness and risk of CVS to a certain extent.…”

Microthrombosis after Aneurysmal Subarachnoid Hemorrhage: An Additional Explanation for Delayed Cerebral Ischemia

“…Consequently, leukocytes can penetrate the vessel wall. Several proinflammatory cytokines, such as interleukin (IL)-1, IL-6, and IL-8, are associated with vasospasm and DCI after SAH (Osuka et al, 1998;Hendryk et al, 2004). It is not completely understood how cytokines lead to ischemia.…”

“…It is not completely understood how cytokines lead to ischemia. Interleukin-6 has vasoconstrictive properties in vitro (Osuka et al, 1998). Cytokines may also indirectly lead to vasoconstriction, for example, by inducing endothelin synthesis or by stimulating the expression of adhesion molecules.…”