Clazosentan, Endothelin-A Receptor Antagonist, Suppresses Interleukin-6 Expression in Cerebrospinal Fluid after Subarachnoid Hemorrhage.

Abstract

Clazosentan (CLA), an endothelin-A receptor antagonist, is used to prevent cerebral vasospasm (CV) following subarachnoid hemorrhage (SAH). Although its efficacy has been demonstrated in large-scale clinical trials, the effects of CLA on cytokine and chemokine profiles in cerebrospinal fluid (CSF) after SAH remain unclear. Twenty-two patients with SAH were enrolled. Ten patients received fasudil hydrochloride (FH), a Rho kinase inhibitor, and 12 received CLA. CSF samples were collected on days 1, 3, 5, 7, 10, and 14. Concentrations of interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP-1), interferon-γ-inducible protein-10 (IP-10), and monokine induced by interferon-γ (MIG) were measured using enzyme-linked immunosorbent assay. IL-6 levels were significantly suppressed during the acute phase in the CLA group compared with the FH group, whereas MCP-1 levels were upregulated on day 1. The peak expression of IP-10 and MIG was delayed in the CLA group relative to the FH group. A strong correlation between IP-10 and MIG was observed on day 5 in the FH group and on day 7 in the CLA group. CLA suppressed IL-6 expression during the acute phase, which may contribute to delayed upregulation of IP-10 and MIG. Suppression of IL-6 may represent a key mechanism underlying the anti-inflammatory effects of CLA following SAH.