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Peer-reviewedCC BY-NC-ND 4.0Neurologia medico-chirurgica

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

  • Toshiaki INOMO1
  • Koji OSUKA1
  • Kenichiro IWAMI1
  • Eiji ITO1
  • Tetsuya IOKU1
  • Tadashi WATANABE1
  1. 1Department of Neurological Surgery, Aichi Medical University, Nagakute, Aichi, Japan
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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.

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Cite

BibTeXRIS
BibTeX
@article{inomo2026clazosentan,
  title = {{Clazosentan, Endothelin-A Receptor Antagonist, Suppresses Interleukin-6 Expression in Cerebrospinal Fluid after Subarachnoid Hemorrhage}},
  author = {Toshiaki INOMO and Koji OSUKA and Kenichiro IWAMI and Eiji ITO and Tetsuya IOKU and Tadashi WATANABE},
  journal = {Neurologia medico-chirurgica},
  year = {2026},
  month = sep,
  doi = {10.2176/jns-nmc.2026-0047},
  url = {https://doi.org/10.2176/jns-nmc.2026-0047},
  note = {CC BY-NC-ND 4.0},
}
RIS
TY  - JOUR
TI  - Clazosentan, Endothelin-A Receptor Antagonist, Suppresses Interleukin-6 Expression in Cerebrospinal Fluid after Subarachnoid Hemorrhage
AU  - Toshiaki INOMO
AU  - Koji OSUKA
AU  - Kenichiro IWAMI
AU  - Eiji ITO
AU  - Tetsuya IOKU
AU  - Tadashi WATANABE
PY  - 2026
DA  - 2026/09/09
JO  - Neurologia medico-chirurgica
DO  - 10.2176/jns-nmc.2026-0047
UR  - https://doi.org/10.2176/jns-nmc.2026-0047
AB  - 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.
SN  - 0470-8105
SN  - 1349-8029
ER  -