Role of cytokines in CNS Diseases.pptx

Role of cytokines in CNS Diseases.pptx

• 1.
  Role Of CytokinesIn CNS Diseases
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  • Recent findingsshown the possibility that inflammatory processes in the brain contribute to the etiopathogenesis of seizures and to the establishment of a chronic epileptic focus. • Prototypical inflammatory cytokines such as IL-1β, TNF-α and IL-6 have been shown to be over expressed in experimental models of seizures in brain areas of seizure generation and propagation, prominently by glia and to a lesser extent by neurons. • Cytokine receptors are upregulated, and the related intracellular signaling is activated. • Cytokines have been shown to profoundly affect seizures in rodents; in particular, IL-1β is endowed of proconvulsant activity in a large variety of seizure models. • The recent demonstration of functional interactions between cytokines and classical neurotransmitters such as glutamate and GABA, suggest the possibility that these interactions underlie the cytokine-mediated changes in neuronal excitability, thus promoting seizure phenomena. Cytokines And Epilepsy
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  • Parkinson's disease(PD) is characterized by degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNpc). • The pro-inflammatory cytokines, IL-1β, TNF-α, IL-2 and IL-6, are expressed at very low levels in healthy brain, but have been found at much higher levels in PD patients, in the post-mortem brain as well as in serum and cerebrospinal fluid in vivo. • The death-signaling receptor, TNFR-1, has been found to be expressed on dopaminergic neurons in human SNpc. • Animal studies support an involvement of these pro-inflammatory cytokines in PD. For example, induction of chronic expression of IL-1β in adult rat SNpc using a recombinant adenovirus resulted in dopaminergic cell death after three weeks. Cytokines And Parkinsonism
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  • Aβ hasbeen shown to increase expression of several cytokine mRNAs. • Over expression of immune modifying cytokine IL-1 by microglia and astrocytes has been shown to occur in AD in brain. • TNF a cytokine produced by microglia that is known to promote cell death in the CNS has been shown to be elevated in AD brain. • Aβ-also have shown to induce production of chemokines in macrophages and in astrocytes. • Different alleles or polymorphisms of a gene may be associated with increased risk of disease. The IL-1A 2,2 genotype of the IL-1 was noted to confer an increased risk for AD in a group of neuropathologically confirmed AD patients. • Another study showed that the interaction between pro-inflammatory IL-6 and anti-inflammatory IL-10 ,was associated with higher risk of AD. Cytokines And Alzheimer's Disease
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  Cytokines in Hematopoiesis
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  • Following focalor global ischaemia, GRO-α and MCP-1 mRNAs are rapidly expressed. • MCP-1 mRNA is initially expressed in astrocytes surrounding the ischaemic tissue and subsequently in infiltrating macrophages and reactive microglia in the infarcted tissue. • Matsumoto et al. showed that IL-8 level is locally produced in reperfused rabbit brain tissue and that a neutralizing anti-IL-8 antibody significantly reduced brain edema and infarct size. Chemokines In Cerebral Ischemia
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  • An upregulationof the CXCR2 protein (receptor for IL-8) occurs in senile plaques adjacent to the hippocampus in the brains of Alzheimer's patients. • Because IL-8 is able to promote survival of hippocampal neurones , a possible involvement of IL-8/CXCR2 in compensatory and reparative mechanisms in the Alzheimer's brain should be considered. • IL-8 mRNA is also known to be regulated by amyloid peptides in human monocytes. Chemokines And Alzheimer's Disease
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  • Multiple sclerosisis a human chronic inflammatory and demyelinating disease that induces subsequent neuronal death. • Acute and chronic-active MS lesions have been shown to be immunoreactive for MCP-1, MCP-2 and MCP-3 throughout the lesion centre (hypertrophic astrocytes and inflammatory cells) while a strong decrease in immunoreactivity was observed at its edge and only hypertrophic astrocytes were reactive for chemokines outside the lesion. • MCP-1 and IL-8 mRNA have also been detected in MS plaques and the levels of MIP-1α, IP-10 and RANTES in the cerebrospinal fluid of MS patients are increased over control values. Chemokines And Multiple Sclerosis
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  • Chemokine expressionis markedly upregulated in healing myocardial infarcts and may play an important role in regulating leukocyte infiltration and activity in modulating infarct angiogenesis as well as fibrous tissue deposition. • The CC-chemokine-monocyte chemo attractant protein-1/CCL2 has important effects in infarct healing. • CXC chemokines are also induced in healing infarcts. • Interleukin-8/CXCL8 may mediate neutrophil recruitment and activation and may promote neovessel formation. • Induction of the angiostatic and antifibrotic chemokine interferon-γ-inducible protein-10/CXCL10 may serve to prevent premature wound angiogenesis and fibrous tissue deposition in the infarct, until the injured myocardium has been cleared from dead cells and debris and a fibrin-rich provisional matrix is formed. • Understanding of the role of chemokines in myocardial ischemia may result in novel strategies in the treatment of patients with ischemic heart disease. Chemokines And Myocardial Ischemia