Soluble gp130 regulatess interleukin-6 in cerebrospinal fluid after subarachnoid haemorrhage.

Abstract

Interleukin-6 (IL-6) is a proinflammatory cytokine reported to play an important role in induction of cerebral vasospasm after subarachnoid haemorrhage (SAH). Soluble gp130 (sgp130) and soluble IL-6 receptor (sIL-6R) are known to act as signal transducing receptors of IL-6, the former as an antagonist and the latter as an agonist. However, there have been no reports concerning regulation of the IL-6 signalling pathway in cerebrospinal fluid (CSF) after SAH. Concentrations of IL-6, sgp130 and sIL-6R were measured serially until day 14 in CSF from nine patients with SAH. CSF samples obtained from patients suffering from unruptured aneurysm were used as controls. Colocalisation of IL-6 and sgp130 in CSF on day 1 was further examined by immunoprecipitaiton. Concentrations of IL-6 in CSF increased immediately after the onset of SAH and remained chronically elevated over control values. Both sgp130 and sIL-6R also exhibited increased on day 1, followed by a decrease limited to the gp130 case after day 5. Sgp130 coimmunoprecipitated with IL-6 in CSF on day 1 after SAH. Our findings suggest that sgp130 regulates IL-6 signalling as an antagonist in CSF immediately after SAH. As the concentration of sgp130 decreases after day 5, IL-6 signals might then be more easily transmitted, presumably resulting in cerebral vasospasm.