Substance P receptor mediated maintenance of chronic inflammation in EAE.
Substance P (SP) is a modulatory, pro-inflammatory neuropeptide. We investigated the role of the SP receptor, neurokinin-1 (NK-1), in EAE. Our data show that in the chronic phase, mice lacking NK-1 have improved mobility and decreased numbers of LFA-1 high CD4+ T cells and MOG-specific, IFN-gamma producing CD4+ T cells. SR140333, an NK-1 antagonist, administered alone during the chronic phase of EAE was not sufficient to ameliorate symptoms. These results indicate that SP, through NK-1, contributes to maintenance of CNS inflammation, and combining NK-1 antagonists with conventional anti-inflammatory treatments may enhance the success of treatments for diseases like multiple sclerosis.
Reinke
Emily K
EK
Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison, Madison WI, United States.
Johnson
Matthew J
MJ
Ling
Changying
C
Karman
Jozsef
J
Lee
Jangeun
J
Weinstock
Joel V
JV
Sandor
Matyas
M
Fabry
Zsuzsa
Z
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002908:Chronic Disease / Q000628:therapy; D004195:Disease Models, Animal; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology* / Q000378:metabolism* / Q000503:physiopathology; D005260:Female; D007111:Immunity, Cellular / Q000187:drug effects / Q000276:immunology; D007165:Immunosuppression Therapy / Q000379:methods / Q000592:standards; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009043:Motor Activity / Q000187:drug effects / Q000276:immunology; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein / Q000276:immunology; D063308:Myelin-Oligodendrocyte Glycoprotein; D015213:Neuroimmunomodulation / Q000276:immunology*; D064729:Neurokinin-1 Receptor Antagonists; D010880:Piperidines / Q000494:pharmacology / Q000627:therapeutic use; D011812:Quinuclidines / Q000494:pharmacology / Q000627:therapeutic use; D018040:Receptors, Neurokinin-1 / Q000235:genetics*; D013373:Substance P / Q000276:immunology*
D000893:Anti-Inflammatory Agents; C571327:Mog protein, mouse; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein; D063308:Myelin-Oligodendrocyte Glycoprotein; D064729:Neurokinin-1 Receptor Antagonists; D010880:Piperidines; D011812:Quinuclidines; D018040:Receptors, Neurokinin-1; C085215:SR 140333; D013373:Substance P; D007371:Interferon-gamma