In multiple sclerosis

The class III cytokine receptor family includes two TNE receptors, the low affinity NGE receptor and 7-ceU surface recognition sites that appear to play a role in proliferation, apoptosis, and immunodeficiency. TNE-a (- 17, 000 protein) is produced by astrocytes and microglia and can induce fever, induce slow-wave sleep, reduce feeding, stimulate prostaglandin synthesis, stimulate corticotrophin-releasing factor and prolactin secretion, and reduce thyroid hormone secretion. TNE-a stimulates IL-1 release, is cytotoxic to oligodendrocytes, and reduces myelination this has been impHcated in multiple sclerosis and encephalomyelitis. Astrocyte TNE-a receptors mediate effects on IL-6 expression and augment astrocytic expression of MHC in response to other stimulants such as lEN-y. 

Interferon beta-la (AVONEX , Rebif ), interferon beta-lb (Betaferon ), and interferon beta (Fiblaferon ) are applied in multiple sclerosis to reduce both frequency and severity of disease incidents and for the treatment of severe viral infections. In multiple sclerosis, DFN- 3 proteins modulate the destruction of myelin in the cause of the autoimmune reaction. 

Selmaj, K., Brosnan, C.F., Raine, C.S. (1991). Colocalization of lymphocytes bearing gamma delta T-cell receptor and heat shock protein hsp65 oligodendrocytes in multiple sclerosis. Proc. Natl. Acad. Sci. USA 88, 6452-6456. 

Phospholipids Sphingolipids Are Involved in Multiple Sclerosis and Lipidoses... 

In multiple sclerosis, which is a demyelinating disease, there is loss of both phospholipids (particularly ethanolamine plasmalogen) and of sphingolipids from white matter. Thus, the lipid composition of white matter resembles that of gray matter. The cerebrospinal fluid shows raised phospholipid levels. 

CCR5 expression likely plays a role in T-cell recruitment and may be involved in the development of autoimmune diseases. There is a negative association between the CCR5A32 mutation and rheumatoid arthritis (Prahalad 2006). Furthermore, additional studies reviewed elsewhere suggest the involvement of CCR5 in multiple sclerosis, diabetes, and transplant rejection (Ribeiro and Horuk 2005). As such, it is likely that CCR5 antagonists developed for the treatment of HIV-1 infection can also be used for other diseases. 

Cheeran MC, Hu S, Sheng WS, Rashid A, Peterson PK, Lokensgard JR (2005) Differential responses of human brain cells to West Nile virus infection. J Neurovirol 11 512-524 Cudrici C, Ito T, Zafranskaia E, Niculescu F, Mullen KM, Vlaicu S, Judge SI, Calabresi PA, Rus H (2007) Dendritic cells are abundant in non-lesional gray matter in multiple sclerosis. Exp Mol Pathol 83 198-206... 

Franklin RJ (2002) Why does remyehnation fail in multiple sclerosis Nat Rev Neurosci 3 705-714 Fratkin JD, Leis AA, Stokic DS, Slavinski SA, Geiss RW (2004) Spinal cord neuropathology in human West Nile virus infection. Arch Pathol Lab Med 128 533-537 Frohman EM, Racke MK, Raine CS (2006) Multiple sclerosis - the plaque and its pathogenesis. N Engl J Med 354 942-955... 

Kmmbholz M, Theil D, Cepok S, Hemmer B, Kivisakk P, Ransohoff RM, Hofbauer M, Farina C, Derfuss T, Hartle C, Newcombe J, Hohlfeld R, Meinl E (2006) Chemokines in multiple sclerosis CXCL12 and CXCL13 up-regulation is differentially linked to CNS immune cell recruitment. Brain 129 200-211... 

McManus C, Berman JW, Brett EM, Staunton H, FarreU M, Brosnan CE (1998) MCP-1, MCP-2 and MCP-3 expression in multiple sclerosis lesions an immunohistochemical and in situ hybridization study. J Neuroimmunol 86 20-29... 

Simpson JE, Newcombe J, Cuzner ML, Woodroofe MN (1998) Expression of monocyte chemoattractant protein-1 and other beta-chemokines by resident glia and inflammatory cells in multiple sclerosis lesions. J Neuroimmunol 84 238-249 Simpson J, Rezaie P, Newcombe J, Cuzner ML, Male D, Woodroofe MN (2000) Expression of the beta-chemokine receptors CCR2, CCR3 and CCR5 in multiple sclerosis central nervous system tissue. J Neuroimmunol 108 192-200... 

Bayas A, Reickmann R Managing the adverse effects of interferon-(3 therapy in multiple sclerosis. Drug Saf 2000 22 149-159. 

DasGupta R, Fowler CJ. Bladder, bowel and sexual dysfunction in multiple sclerosis management strategies. Drugs 2003 63 153-166. 

Goodin DS, Frohman EM, Garmany GR et al. Disease modifying therapies in multiple sclerosis report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology and the MS Council for Clinical Practice Guidelines. Neurology 2002 58 169-178. 

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