Araştırma Makalesi
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Effects of Tumor Necrosis Factor Alpha Blocker Adalimumab in Experimental Brain Injury

Yıl 2019, Cilt 3, Sayı 3, 306 - 310, 26.10.2019
https://doi.org/10.30565/medalanya.632455

Öz

Aim: We aimed to investigate the neuroprotective role of adalimumab based on the hypothesis that "TNF-alpha inhibitor Adalimumab may affect inflammation-related neuronal injury due to its anti-inflammatory effect". 

Methods: To investigate the effects of Adalimumab, we induced brain injury in mice using a cold trauma model and evaluated the underlying cell survival/ death mechanisms via cresyl violet and calculated infarct/edema volume with image analyze system. 

Results: Although our data indicated a tendency to decreased infarct and edema volume, these findings are not significant statistically. 

Conclusion: To the best of our knowledge, this is the first study evaluating the neuroprotective effect of Adalimumab on injured neurons. 

Kaynakça

  • 1. Narayan RK, Michel ME, Ansell B, Baethmann A, Biegon A, Bracken MB, et al. Clinical trials in head injury. Journal of neurotrauma. 2002;19(5):503-57. doi: 10.1089/089771502753754037.
  • 2. Maas AI, Roozenbeek B, Manley GT. Clinical trials in traumatic brain injury: past experience and current developments. Neurotherapeutics. 2010;7(1):115-26. doi: 10.1016/j.nurt.2009.10.022.
  • 3. Werner C, Engelhard K. Pathophysiology of traumatic brain injury. Br J Anaesth. 2007;99(1):4-9. doi: 10.1093/bja/aem131.
  • 4. Burmester GR, Mease P, Dijkmans BA, Gordon K, Lovell D, Panaccione R, et al. Adalimumab safety and mortality rates from global clinical trials of six immune-mediated inflammatory diseases. Ann Rheum Dis. 2009;68(12):1863-9.  doi: 10.1136/ard.2008.102103.
  • 5. Clark J, Vagenas P, Panesar M, Cope AP. What does tumour necrosis factor excess do to the immune system long term? Annals of the Rheumatic Diseases. 2005;64:70-6. doi: 10.1136/ard.2005.042523.
  • 6. Woodcock T, Morganti-Kossmann MC. The role of markers of inflammation in traumatic brain injury. Front Neurol. 2013;4:18. doi: 10.3389/fneur.2013.00018.
  • 7. Mitoma H, Horiuchi T, Tsukamoto H, Ueda N. Molecular mechanisms of action of anti-TNF-alpha agents - Comparison among therapeutic TNF-alpha antagonists. Cytokine. 2018;101:56-63. doi: 10.1016/j.cyto.2016.08.014.
  • 8. Shohet JM, Bergamaschini L, Davis AE, Carroll MC. Localization of the human complement component C3 binding site on the IgG heavy chain. J Biol Chem. 1991;266(28):18520-4. PMID: 1917974
  • 9. Tracey D, Klareskog L, Sasso EH, Salfeld JG, Tak PP. Tumor necrosis factor antagonist mechanisms of action: a comprehensive review. Pharmacol Ther. 2008;117(2):244-79. doi: 10.1016/j.pharmthera.2007.10.001
  • 10. Yu F, Gudmundsdotter L, Akal A, Gunneriusson E, Frejd F, Nygren PA. An affibody-adalimumab hybrid blocks combined IL-6 and TNF-triggered serum amyloid A secretion in vivo. MAbs. 2014;6(6):1598-607. doi: 10.4161/mabs.36089.
  • 11. Yan HY, Semple KM, Gonzalez CM, Howard KE. Bone marrow-liver-thymus (BLT) immune humanized mice as a model to predict cytokine release syndrome. Transl Res. 2019;210:43-56. doi: 10.1016/j.trsl.2019.04.007. 
  • 12. Park J, Lee SY, Shon J, Kim K, Lee HJ, Kim KA, et al. Adalimumab improves cognitive impairment, exerts neuroprotective effects and attenuates neuroinflammation in an A beta(1-40)-injected mouse model of Alzheimer's disease. Cytotherapy. 2019;21(6):671-82. doi: 10.1016/j.jcyt.2019.04.054.
  • 13. Ubah OC, Steven J, Porter AJ, Barelle CJ. An Anti-hTNF-alpha Variable New Antigen Receptor Format Demonstrates Superior in vivo Preclinical Efficacy to Humira(R) in a Transgenic Mouse Autoimmune Polyarthritis Disease Model. Front Immunol. 2019;10:526. doi: 10.3389/fimmu.2019.00526. 
  • 14. Hermann DM, Kilic E, Kügler S, Isenmann S, Bähr M. Adenovirus-mediated glial cell line-derived neurotrophic factor (GDNF) expression protects against subsequent cortical cold injury in rats. Neurobiology of disease. 2001;8(6):964-73. doi: 10.1006/nbdi.2001.0448.
  • 15. Keskin I, Gunal MY, Ayturk N, Kilic U, Ozansoy M, Kilic E. Dose-dependent neuroprotective effect of enoxaparin on cold-induced traumatic brain injury. Neural regeneration research. 2017;12(5):761. doi: 10.4103/1673-5374.206646.
  • 16. Alvarez-Buylla A, Vicario DS. Simple microcomputer system for mapping tissue sections with the light microscope. Journal of neuroscience methods. 1988;25(2):165-73. doi: 10.1016/0165-0270(88)90155-0
  • 17. Ramilo O, Sáez-Llorens X, Mertsola J, Jafari H, Olsen KD, Hansen EJ, et al. Tumor necrosis factor alpha/cachectin and interleukin 1 beta initiate meningeal inflammation. Journal of Experimental Medicine. 1990;172(2):497-507. doi: 10.1084/jem.172.2.497.
  • 18. Kim KS, Wass C, Cross A, Opal S. Modulation of blood-brain barrier permeability by tumor necrosis factor and antibody to tumor necrosis factor in the rat. Lymphokine and cytokine research. 1992;11(6):293-8. PMID: 1477182
  • 19. Shohami E, Bass R, Wallach D, Yamin A, Gallily R. Inhibition of tumor necrosis factor alpha (TNFα) activity in rat brain is associated with cerebroprotection after closed head injury. Journal of Cerebral Blood Flow & Metabolism. 1996;16(3):378-84. doi: 10.1097/00004647-199605000-00004.
  • 20. Knoblach SM, Fan L, Faden AI. Early neuronal expression of tumor necrosis factor-α after experimental brain injury contributes to neurological impairment. Journal of neuroimmunology. 1999;95(1-2):115-25. doi: 10.1016/s0165-5728(98)00273-2.
  • 21. Scherbel U, Raghupathi R, Nakamura M, Saatman KE, Trojanowski JQ, Neugebauer E, et al. Differential acute and chronic responses of tumor necrosis factor-deficient mice to experimental brain injury. Proceedings of the National Academy of Sciences. 1999;96(15):8721-6. doi: 10.1073/pnas.96.15.8721
  • 22. Sullivan PG, Bruce-Keller AJ, Rabchevsky AG, Christakos S, Clair DKS, Mattson MP, et al. Exacerbation of damage and altered NF-κB activation in mice lacking tumor necrosis factor receptors after traumatic brain injury. Journal of Neuroscience. 1999;19(15):6248-56. PMID: 10414954
  • 23. Morganti-Kossman M, Lenzlinger P, Hans V, Stahel P, Csuka E, Ammann E, et al. Production of cytokines following brain injury: beneficial and deleterious for the damaged tissue. Molecular psychiatry. 1997;2(2):133-6. PMID: 9106236
  • 24. Lenzlinger PM, Morganti-Kossmann M-C, Laurer HL, McIntosh TK. The duality of the inflammatory response to traumatic brain injury. Molecular neurobiology. 2001;24(1-3):169-81. doi: 10.1385/MN:24:1-3:169.
  • 25. Azevedo VF, Troiano LDC, Galli NB, Kleinfelder A, Catolino NM, Martins PCU. Adalimumab: A review of the reference product and biosimilars. Biosimilars. 2016;6:29-44. doi: 10.2147/BS.S98177.

Tümör Nekroz Faktörü Alfa Blokeri Adalimumabın Deneysel Beyin Hasarında Etkileri

Yıl 2019, Cilt 3, Sayı 3, 306 - 310, 26.10.2019
https://doi.org/10.30565/medalanya.632455

Öz

Amaç: “TNF-alfa inhibitörü Adalimumab’ın, anti-inflamatuvar etkisi nedeniyle inflamasyonla ilişkili nöronal hasarı etkileyebileceği” hipotezine dayanarak Adalimumab’ın nöroprotektif rolünü araştırmayı amaçladık. 

Metotlar: Adalimumab’ın etkilerini araştırmak için soğuk travma modelini kullanarak farelerde beyin hasarı oluşturduk ve krezil viyole boyasıyla hücre sağ-kalım/ölüm oranları ile görüntü analiz sistemi ile hesaplanan infarktüs/ödem hacmini değerlendirdik. 

Bulgular: Verilerimiz infarkt ve ödem hacminde azalma eğilimi göstermesine rağmen istatistiksel olarak anlamlı değildir. 

Sonuç: Bildiğimiz kadarıyla çalışmamız Adalimumab’ın hasarlı nöronlar üzerindeki nöroprotektif etkisini değerlendiren ilk çalışmadır. 

Kaynakça

  • 1. Narayan RK, Michel ME, Ansell B, Baethmann A, Biegon A, Bracken MB, et al. Clinical trials in head injury. Journal of neurotrauma. 2002;19(5):503-57. doi: 10.1089/089771502753754037.
  • 2. Maas AI, Roozenbeek B, Manley GT. Clinical trials in traumatic brain injury: past experience and current developments. Neurotherapeutics. 2010;7(1):115-26. doi: 10.1016/j.nurt.2009.10.022.
  • 3. Werner C, Engelhard K. Pathophysiology of traumatic brain injury. Br J Anaesth. 2007;99(1):4-9. doi: 10.1093/bja/aem131.
  • 4. Burmester GR, Mease P, Dijkmans BA, Gordon K, Lovell D, Panaccione R, et al. Adalimumab safety and mortality rates from global clinical trials of six immune-mediated inflammatory diseases. Ann Rheum Dis. 2009;68(12):1863-9.  doi: 10.1136/ard.2008.102103.
  • 5. Clark J, Vagenas P, Panesar M, Cope AP. What does tumour necrosis factor excess do to the immune system long term? Annals of the Rheumatic Diseases. 2005;64:70-6. doi: 10.1136/ard.2005.042523.
  • 6. Woodcock T, Morganti-Kossmann MC. The role of markers of inflammation in traumatic brain injury. Front Neurol. 2013;4:18. doi: 10.3389/fneur.2013.00018.
  • 7. Mitoma H, Horiuchi T, Tsukamoto H, Ueda N. Molecular mechanisms of action of anti-TNF-alpha agents - Comparison among therapeutic TNF-alpha antagonists. Cytokine. 2018;101:56-63. doi: 10.1016/j.cyto.2016.08.014.
  • 8. Shohet JM, Bergamaschini L, Davis AE, Carroll MC. Localization of the human complement component C3 binding site on the IgG heavy chain. J Biol Chem. 1991;266(28):18520-4. PMID: 1917974
  • 9. Tracey D, Klareskog L, Sasso EH, Salfeld JG, Tak PP. Tumor necrosis factor antagonist mechanisms of action: a comprehensive review. Pharmacol Ther. 2008;117(2):244-79. doi: 10.1016/j.pharmthera.2007.10.001
  • 10. Yu F, Gudmundsdotter L, Akal A, Gunneriusson E, Frejd F, Nygren PA. An affibody-adalimumab hybrid blocks combined IL-6 and TNF-triggered serum amyloid A secretion in vivo. MAbs. 2014;6(6):1598-607. doi: 10.4161/mabs.36089.
  • 11. Yan HY, Semple KM, Gonzalez CM, Howard KE. Bone marrow-liver-thymus (BLT) immune humanized mice as a model to predict cytokine release syndrome. Transl Res. 2019;210:43-56. doi: 10.1016/j.trsl.2019.04.007. 
  • 12. Park J, Lee SY, Shon J, Kim K, Lee HJ, Kim KA, et al. Adalimumab improves cognitive impairment, exerts neuroprotective effects and attenuates neuroinflammation in an A beta(1-40)-injected mouse model of Alzheimer's disease. Cytotherapy. 2019;21(6):671-82. doi: 10.1016/j.jcyt.2019.04.054.
  • 13. Ubah OC, Steven J, Porter AJ, Barelle CJ. An Anti-hTNF-alpha Variable New Antigen Receptor Format Demonstrates Superior in vivo Preclinical Efficacy to Humira(R) in a Transgenic Mouse Autoimmune Polyarthritis Disease Model. Front Immunol. 2019;10:526. doi: 10.3389/fimmu.2019.00526. 
  • 14. Hermann DM, Kilic E, Kügler S, Isenmann S, Bähr M. Adenovirus-mediated glial cell line-derived neurotrophic factor (GDNF) expression protects against subsequent cortical cold injury in rats. Neurobiology of disease. 2001;8(6):964-73. doi: 10.1006/nbdi.2001.0448.
  • 15. Keskin I, Gunal MY, Ayturk N, Kilic U, Ozansoy M, Kilic E. Dose-dependent neuroprotective effect of enoxaparin on cold-induced traumatic brain injury. Neural regeneration research. 2017;12(5):761. doi: 10.4103/1673-5374.206646.
  • 16. Alvarez-Buylla A, Vicario DS. Simple microcomputer system for mapping tissue sections with the light microscope. Journal of neuroscience methods. 1988;25(2):165-73. doi: 10.1016/0165-0270(88)90155-0
  • 17. Ramilo O, Sáez-Llorens X, Mertsola J, Jafari H, Olsen KD, Hansen EJ, et al. Tumor necrosis factor alpha/cachectin and interleukin 1 beta initiate meningeal inflammation. Journal of Experimental Medicine. 1990;172(2):497-507. doi: 10.1084/jem.172.2.497.
  • 18. Kim KS, Wass C, Cross A, Opal S. Modulation of blood-brain barrier permeability by tumor necrosis factor and antibody to tumor necrosis factor in the rat. Lymphokine and cytokine research. 1992;11(6):293-8. PMID: 1477182
  • 19. Shohami E, Bass R, Wallach D, Yamin A, Gallily R. Inhibition of tumor necrosis factor alpha (TNFα) activity in rat brain is associated with cerebroprotection after closed head injury. Journal of Cerebral Blood Flow & Metabolism. 1996;16(3):378-84. doi: 10.1097/00004647-199605000-00004.
  • 20. Knoblach SM, Fan L, Faden AI. Early neuronal expression of tumor necrosis factor-α after experimental brain injury contributes to neurological impairment. Journal of neuroimmunology. 1999;95(1-2):115-25. doi: 10.1016/s0165-5728(98)00273-2.
  • 21. Scherbel U, Raghupathi R, Nakamura M, Saatman KE, Trojanowski JQ, Neugebauer E, et al. Differential acute and chronic responses of tumor necrosis factor-deficient mice to experimental brain injury. Proceedings of the National Academy of Sciences. 1999;96(15):8721-6. doi: 10.1073/pnas.96.15.8721
  • 22. Sullivan PG, Bruce-Keller AJ, Rabchevsky AG, Christakos S, Clair DKS, Mattson MP, et al. Exacerbation of damage and altered NF-κB activation in mice lacking tumor necrosis factor receptors after traumatic brain injury. Journal of Neuroscience. 1999;19(15):6248-56. PMID: 10414954
  • 23. Morganti-Kossman M, Lenzlinger P, Hans V, Stahel P, Csuka E, Ammann E, et al. Production of cytokines following brain injury: beneficial and deleterious for the damaged tissue. Molecular psychiatry. 1997;2(2):133-6. PMID: 9106236
  • 24. Lenzlinger PM, Morganti-Kossmann M-C, Laurer HL, McIntosh TK. The duality of the inflammatory response to traumatic brain injury. Molecular neurobiology. 2001;24(1-3):169-81. doi: 10.1385/MN:24:1-3:169.
  • 25. Azevedo VF, Troiano LDC, Galli NB, Kleinfelder A, Catolino NM, Martins PCU. Adalimumab: A review of the reference product and biosimilars. Biosimilars. 2016;6:29-44. doi: 10.2147/BS.S98177.

Ayrıntılar

Birincil Dil İngilizce
Konular Tıp
Yayınlanma Tarihi 2019-3
Bölüm Araştırma Makalesi
Yazarlar

Mehmet Yalçın GÜNAL (Sorumlu Yazar)
ALANYA ALAADDIN KEYKUBAT UNIVERSITY, FACULTY OF MEDICINE
0000-0001-7702-2441
Türkiye


Seyda CANKAYA
ALANYA ALAADDIN KEYKUBAT UNIVERSITY, FACULTY OF MEDICINE
0000-0001-5309-0351
Türkiye


Sukru Burak TONUK
ABANT IZZET BAYSAL UNIVERSITY, FACULTY OF MEDICINE
0000-0003-0290-9341
Türkiye


Ekrem Musa OZDEMİR Bu kişi benim
ISTANBUL MEDIPOL UNIVERSITY
0000-0001-9416-7757
Türkiye


Ayse Arzu SAYIN SAKUL Bu kişi benim
FACULTY OF MEDICINE
0000-0002-9354-0000
Türkiye

Yayımlanma Tarihi 26 Ekim 2019
Başvuru Tarihi 12 Ekim 2019
Kabul Tarihi 20 Ekim 2019
Yayınlandığı Sayı Yıl 2019, Cilt 3, Sayı 3

Kaynak Göster

Vancouver Günal M. Y. , Cankaya S. , Tonuk S. B. , Ozdemir E. M. , Sayın Sakul A. A. Effects of Tumor Necrosis Factor Alpha Blocker Adalimumab in Experimental Brain Injury. Acta Medica Alanya. 2019; 3(3): 306-310.

9705 

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