The Comparative Effects of Anakinra and Tocilizumab on Inflammation and Cerebral Vasospasm in an Experimental Subarachnoid Hemorrhage Model
<i>Objective</i>: Subarachnoid hemorrhage (SAH) is a life-threatening cerebrovascular condition that triggers a robust inflammatory response and cerebral vasospasm. This study aimed to evaluate the effects of anakinra, an interleukin-1 receptor antagonist, and tocilizumab, an interleukin...
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2024-12-01
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| author | Güven Kılıç Berk Enes Engin Amir Halabi Cengiz Tuncer Mehmet Ali Sungur Merve Alpay Adem Kurtuluş Hakan Soylu Ali Gök |
| author_facet | Güven Kılıç Berk Enes Engin Amir Halabi Cengiz Tuncer Mehmet Ali Sungur Merve Alpay Adem Kurtuluş Hakan Soylu Ali Gök |
| author_sort | Güven Kılıç |
| collection | DOAJ |
| description | <i>Objective</i>: Subarachnoid hemorrhage (SAH) is a life-threatening cerebrovascular condition that triggers a robust inflammatory response and cerebral vasospasm. This study aimed to evaluate the effects of anakinra, an interleukin-1 receptor antagonist, and tocilizumab, an interleukin-6 receptor antagonist, on inflammation and vasospasm in an experimental rat SAH model. <i>Methods</i>: Forty male Sprague Dawley rats (200–250 g) were randomly assigned to five groups: control, SAH, SAH + anakinra (ANA), SAH + tocilizumab (TCZ), and SAH + anakinra + tocilizumab (ANA+TCZ). SAH was induced by injecting non-heparinized arterial blood into the cisterna magna. Treatment groups received anakinra (50 mg/kg twice daily), tocilizumab (8 mg/kg once daily), or their combination for three days. Blood and cerebrospinal fluid (CSF) samples were analyzed for inflammatory markers (IL-1, IL-6, TNF-α, CRP), and histopathological evaluations were conducted to assess vasospasm and apoptosis. <i>Results</i>: SAH significantly increased pro-inflammatory cytokines (IL-1, IL-6, TNF-α, CRP) and fibrinogen levels in serum and CSF while reducing the basilar artery lumen diameter (<i>p</i> < 0.001). Anakinra and tocilizumab treatments significantly reduced inflammatory markers and vasospasm severity compared to the SAH group (<i>p</i> < 0.05). Combination therapy was more effective in reducing inflammation and vasospasm than either treatment alone (<i>p</i> < 0.05). Anakinra showed a stronger effect on IL-1 reduction, while tocilizumab was more effective in lowering IL-6 levels. The ANA+TCZ group exhibited a significant decrease in caspase activity, indicating reduced apoptosis (<i>p</i> < 0.05). <i>Conclusions</i>: Anakinra and tocilizumab effectively mitigated inflammation and vasospasm in an experimental SAH model, with combination therapy showing superior efficacy. These findings suggest that targeting both IL-1 and IL-6 pathways may be a promising therapeutic strategy for managing SAH complications. Further studies are warranted to evaluate long-term outcomes and clinical implications. |
| format | Article |
| id | doaj-art-cc2aba4eb63d4afaac65dcb02d066606 |
| institution | DOAJ |
| issn | 1010-660X 1648-9144 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | MDPI AG |
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| series | Medicina |
| spelling | doaj-art-cc2aba4eb63d4afaac65dcb02d0666062025-08-20T02:39:41ZengMDPI AGMedicina1010-660X1648-91442024-12-016012202510.3390/medicina60122025The Comparative Effects of Anakinra and Tocilizumab on Inflammation and Cerebral Vasospasm in an Experimental Subarachnoid Hemorrhage ModelGüven Kılıç0Berk Enes Engin1Amir Halabi2Cengiz Tuncer3Mehmet Ali Sungur4Merve Alpay5Adem Kurtuluş6Hakan Soylu7Ali Gök8Department of Neurosurgery, Faculty of Medicine, Duzce University, Duzce 81100, TürkiyeDepartment of Neurosurgery, Faculty of Medicine, Duzce University, Duzce 81100, TürkiyeDepartment of Neurosurgery, Faculty of Medicine, Duzce University, Duzce 81100, TürkiyeDepartment of Neurosurgery, Faculty of Medicine, Duzce University, Duzce 81100, TürkiyeDepartment of Biostatistics, Faculty of Medicine, Duzce University, Duzce 81100, TürkiyeDepartment of Biochemistry and Molecular Biology, Faculty of Medicine, Duzce University, Duzce 81100, TürkiyeDepartment of Neurosurgery, Faculty of Medicine, Duzce University, Duzce 81100, TürkiyeDepartment of Histology and Embryology, Faculty of Medicine, Duzce University, Duzce 81100, TürkiyeExperimental Animals Application and Research Center, Duzce University, Duzce 81100, Türkiye<i>Objective</i>: Subarachnoid hemorrhage (SAH) is a life-threatening cerebrovascular condition that triggers a robust inflammatory response and cerebral vasospasm. This study aimed to evaluate the effects of anakinra, an interleukin-1 receptor antagonist, and tocilizumab, an interleukin-6 receptor antagonist, on inflammation and vasospasm in an experimental rat SAH model. <i>Methods</i>: Forty male Sprague Dawley rats (200–250 g) were randomly assigned to five groups: control, SAH, SAH + anakinra (ANA), SAH + tocilizumab (TCZ), and SAH + anakinra + tocilizumab (ANA+TCZ). SAH was induced by injecting non-heparinized arterial blood into the cisterna magna. Treatment groups received anakinra (50 mg/kg twice daily), tocilizumab (8 mg/kg once daily), or their combination for three days. Blood and cerebrospinal fluid (CSF) samples were analyzed for inflammatory markers (IL-1, IL-6, TNF-α, CRP), and histopathological evaluations were conducted to assess vasospasm and apoptosis. <i>Results</i>: SAH significantly increased pro-inflammatory cytokines (IL-1, IL-6, TNF-α, CRP) and fibrinogen levels in serum and CSF while reducing the basilar artery lumen diameter (<i>p</i> < 0.001). Anakinra and tocilizumab treatments significantly reduced inflammatory markers and vasospasm severity compared to the SAH group (<i>p</i> < 0.05). Combination therapy was more effective in reducing inflammation and vasospasm than either treatment alone (<i>p</i> < 0.05). Anakinra showed a stronger effect on IL-1 reduction, while tocilizumab was more effective in lowering IL-6 levels. The ANA+TCZ group exhibited a significant decrease in caspase activity, indicating reduced apoptosis (<i>p</i> < 0.05). <i>Conclusions</i>: Anakinra and tocilizumab effectively mitigated inflammation and vasospasm in an experimental SAH model, with combination therapy showing superior efficacy. These findings suggest that targeting both IL-1 and IL-6 pathways may be a promising therapeutic strategy for managing SAH complications. Further studies are warranted to evaluate long-term outcomes and clinical implications.https://www.mdpi.com/1648-9144/60/12/2025subarachnoid hemorrhageanakinratocilizumabvasospasminflammationinterleukin-1 |
| spellingShingle | Güven Kılıç Berk Enes Engin Amir Halabi Cengiz Tuncer Mehmet Ali Sungur Merve Alpay Adem Kurtuluş Hakan Soylu Ali Gök The Comparative Effects of Anakinra and Tocilizumab on Inflammation and Cerebral Vasospasm in an Experimental Subarachnoid Hemorrhage Model Medicina subarachnoid hemorrhage anakinra tocilizumab vasospasm inflammation interleukin-1 |
| title | The Comparative Effects of Anakinra and Tocilizumab on Inflammation and Cerebral Vasospasm in an Experimental Subarachnoid Hemorrhage Model |
| title_full | The Comparative Effects of Anakinra and Tocilizumab on Inflammation and Cerebral Vasospasm in an Experimental Subarachnoid Hemorrhage Model |
| title_fullStr | The Comparative Effects of Anakinra and Tocilizumab on Inflammation and Cerebral Vasospasm in an Experimental Subarachnoid Hemorrhage Model |
| title_full_unstemmed | The Comparative Effects of Anakinra and Tocilizumab on Inflammation and Cerebral Vasospasm in an Experimental Subarachnoid Hemorrhage Model |
| title_short | The Comparative Effects of Anakinra and Tocilizumab on Inflammation and Cerebral Vasospasm in an Experimental Subarachnoid Hemorrhage Model |
| title_sort | comparative effects of anakinra and tocilizumab on inflammation and cerebral vasospasm in an experimental subarachnoid hemorrhage model |
| topic | subarachnoid hemorrhage anakinra tocilizumab vasospasm inflammation interleukin-1 |
| url | https://www.mdpi.com/1648-9144/60/12/2025 |
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