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Impact of sphingosine 1-phosphate modulation on immune outcomes.
Neurology 2011; 76(8 Suppl 3):S15-9Neur

Abstract

Viral infections may have an important role in the precipitation or relapse of multiple sclerosis (MS) and its treatment. This review describes the normal immune response to viral infection, the possible associations between viral infections and MS therapy, and the impact of sphingosine 1-phosphate (S1P) receptor (S1PR) modulation with fingolimod (FTY720) on the immune responses to viral infection. The physiologic immune response to viral infection involves lymphocyte activation and control of the circulation of subsets of lymphocytes with different functions between the lymph nodes, vascular system, and tissues, under the control of the S1P/S1PR signaling mechanism. In MS, it has been postulated that viral infections may play a role in triggering MS relapses, with virus-specific T cells being responsible for the demyelinating lesions within the CNS. Fingolimod-an S1PR modulator approved for the treatment of relapsing MS in some countries-is thought to act by downmodulating lymphatic S1P subtype 1 receptors. This retains naïve T cells and central memory T cells, but not effector memory T cells, within the lymph nodes and prevents their circulation to the CNS. Evidence from infection models supports that the selective effects of fingolimod on T cell subsets allows key immune responses to be preserved during therapy. However, in patients, long-term observation is important as both the risk of cancer and infection is potentially increased by the use of any immunomodulatory agent.

Authors+Show Affiliations

Department of Pathology and Immunology, University of Geneva, Geneva.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Review

Language

eng

PubMed ID

21339486

Citation

Pinschewer, Daniel D., et al. "Impact of Sphingosine 1-phosphate Modulation On Immune Outcomes." Neurology, vol. 76, no. 8 Suppl 3, 2011, pp. S15-9.
Pinschewer DD, Brinkmann V, Merkler D. Impact of sphingosine 1-phosphate modulation on immune outcomes. Neurology. 2011;76(8 Suppl 3):S15-9.
Pinschewer, D. D., Brinkmann, V., & Merkler, D. (2011). Impact of sphingosine 1-phosphate modulation on immune outcomes. Neurology, 76(8 Suppl 3), pp. S15-9. doi:10.1212/WNL.0b013e31820d9596.
Pinschewer DD, Brinkmann V, Merkler D. Impact of Sphingosine 1-phosphate Modulation On Immune Outcomes. Neurology. 2011 Feb 22;76(8 Suppl 3):S15-9. PubMed PMID: 21339486.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Impact of sphingosine 1-phosphate modulation on immune outcomes. AU - Pinschewer,Daniel D, AU - Brinkmann,Volker, AU - Merkler,Doron, PY - 2011/2/23/entrez PY - 2011/2/26/pubmed PY - 2011/3/12/medline SP - S15 EP - 9 JF - Neurology JO - Neurology VL - 76 IS - 8 Suppl 3 N2 - Viral infections may have an important role in the precipitation or relapse of multiple sclerosis (MS) and its treatment. This review describes the normal immune response to viral infection, the possible associations between viral infections and MS therapy, and the impact of sphingosine 1-phosphate (S1P) receptor (S1PR) modulation with fingolimod (FTY720) on the immune responses to viral infection. The physiologic immune response to viral infection involves lymphocyte activation and control of the circulation of subsets of lymphocytes with different functions between the lymph nodes, vascular system, and tissues, under the control of the S1P/S1PR signaling mechanism. In MS, it has been postulated that viral infections may play a role in triggering MS relapses, with virus-specific T cells being responsible for the demyelinating lesions within the CNS. Fingolimod-an S1PR modulator approved for the treatment of relapsing MS in some countries-is thought to act by downmodulating lymphatic S1P subtype 1 receptors. This retains naïve T cells and central memory T cells, but not effector memory T cells, within the lymph nodes and prevents their circulation to the CNS. Evidence from infection models supports that the selective effects of fingolimod on T cell subsets allows key immune responses to be preserved during therapy. However, in patients, long-term observation is important as both the risk of cancer and infection is potentially increased by the use of any immunomodulatory agent. SN - 1526-632X UR - https://www.unboundmedicine.com/medline/citation/21339486/Impact_of_sphingosine_1_phosphate_modulation_on_immune_outcomes_ L2 - http://www.neurology.org/cgi/pmidlookup?view=long&pmid=21339486 DB - PRIME DP - Unbound Medicine ER -