Tumour Necrosis Factor alpha - TNF

Tumour Necrosis Factor alpha - TNF

  • Tumor Necrosis Factor - alpha (TNFα) is a cytokine produced by white blood cells which acts as the master regulator of the human inflammatory response.

  • Proinflammatory tumor necrosis factor-alpha (TNF) is a key mediator of neuropathic pain pathogenesis; TNF is elevated at sites of neuronal injury, in the spinal cord, and supraspinally during the initial development of pain.

  • Chronic, neuropathic pain includes elevated levels of the cytokine tumor necrosis factor-alpha (TNF). The hippocampus, an area of the brain most notable for its role in learning and memory formation, plays a fundamental role in pain sensation.

  • Neurogenesis refers to the growth and development of neurons.  Research has shown that the human hippocampus retains its ability to generate neurons throughout life.

  • Elevated levels of TNF in the Hippocampal region leads to atrophy and is associated with many brain diseases, including depression, psychosis, addiction and dementia.

  • Animal studies demonstrate that infusion of an anti -TNFα agent adjacent to the hippocampus completely alleviated pain.

  • Elevated pro-inflammatory markers Cytokines (IL1, IL6, IL7, IL8) and TNFα are linked with chronic and progressive neurodegenerative disease - often referred to as a Cytokine Storm leading to multisystem inflammatory cascade (autoimmune erosion). The body due to autoimmune dysfunction - attacks itself!

Supporting evidence for using (product named removed) anti-TNF therapies to inhibit TNFα when treating neuropathologies including dementia, chronic stroke, neuropathic pain or traumatic brain injury: Clinical outcomes and role of TNF in neuropathologies other than Alzheimer’s Dementia

S Ralph (Griffith University Queensland)

Part III examines the evidence for the involvement of the pro-inflammatory cytokine, Tumour Necrosis Factor alpha (TNFα) in neuropathologies other than Alzheimer’s Dementia (AD), and for using an anti-TNF therapy, to target and treat these health problems, including chronic stroke, neuropathic pain or traumatic brain injury (TBI).

All of these can become chronic illnesses and are of major incidence with a grossly unmet need to improve their treatment. The three-part review presents the overwhelming scientific and medical basis as to why research studies and more trials to evaluate the use of the perispinally administered anti-TNFα drug, are justified to allow it to become a front-line standard therapy.

Part I established the role of TNFα as a direct regulator of neuronal synaptic activity. It is in this context, as detailed below, that targeting TNF in the brain holds major significance, not only for treating the dementias, but also its great benefits in reducing long term pain during rehabilitation from TBI or chronic stroke.

Given the increasing numbers of families afflicted with Alzheimer’s disease, chronic stroke, neuropathic pain or TBI, clinical studies are now imperative to improve the treatment of these life-threatening and debilitating illnesses. 

What Are The Effects of TNF-alpha in Neurologic Disorders?

 

  • Excess TNF-alpha in the brain and spinal cord can disrupt synaptic communication.

  • Excess TNF-alpha triggers a cycle whereby toxic amyloid-beta is produced. This results in greater levels of pro-inflammatory TNF-alpha.

  • Increasing amounts of laboratory evidence implicate TNF-alpha in inflammatory molecular mechanisms producing neurotoxicity, neuronal death, or neuronal dysfunction.

  • Elevated TNF-alpha has been linked with many neurovascular and autoimmune disorders.

Anti TNFα Therapies 

Anti-TNFα therapies are developed to treat various inflammatory diseases by binding to TNF-alpha, effectively neutralizing its ability to act on cell membranes.

Brain Neurovascular Inflammation
Chronic Pain
Autoimmune Disorders
Articles by Tobinick et al

 

http://www.ncbi.nlm.nih.gov/pubmed/19689163

Tumour necrosis factor modulation for treatment of Alzheimer's disease: rationale and current evidence.

Tobinick E.
CNS Drugs. 2009 Sep 1;23(9):713-25. doi: 10.2165/11310810-000000000-00000. Review.
PMID: 19689163 [PubMed - indexed for MEDLINE]


Tumour necrosis factor modulation for neuroinflammatory disorders.

Tobinick E.
Drug Discov Today. 2009 Feb;14(3-4):168-77. Epub 2008 Dec 6. Review.
PMID: 19027875 [PubMed - indexed for MEDLINE]
 

Rapid improvement in verbal fluency and aphasia following Tumour necrosis factor modulation in Alzheimer's disease.

Tobinick EL, Gross H.
BMC Neurol. 2008 Jul 21;8:27.
PMID: 18644112 [PubMed - indexed for MEDLINE]Free PMC ArticleFree text
 

Inflammatory markers and the risk of Alzheimer disease: the Framingham Study.

Tobinick EL.
Neurology. 2008 Apr 1;70(14):1222-3; author reply 1223. No abstract available.
PMID: 18378889 [PubMed - indexed for MEDLINE]
 

Tumour necrosis factor modulation for treatment of Alzheimer's disease.

Tobinick E.
Curr Alzheimer Res. 2007 Dec;4(5):550-2. Review.
PMID: 18220520 [PubMed - indexed for MEDLINE]
 

Rapid cognitive improvement in Alzheimer's disease following Tumour necrosis factor modulation administration.

Tobinick EL, Gross H.
J Neuroinflammation. 2008 Jan 9;5:2.
PMID: 18184433 [PubMed - indexed for MEDLINE]Free PMC ArticleFree text
 

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