title: Inhibition of SLPI ameliorates disease activity in experimental autoimmune encephalomyelitis.
abstract: BACKGROUND
  The secretory leukocyte protease inhibitor (SLPI) exerts wide ranging effects on inflammatory pathways and is upregulated in EAE but the biological role of SLPI in EAE, an animal model of multiple sclerosis is unknown
  
  
  METHODS
  To investigate the pathophysiological effects of SLPI within EAE, we induced SLPI-neutralizing antibodies in mice and rats to determine the clinical severity of the disease. In addition we studied the effects of SLPI on the anti-inflammatory cytokine TGF-β.
  
  
  RESULTS
  The induction of SLPI neutralizing antibodies resulted in a milder disease course in mouse and rat EAE. SLPI neutralization was associated with increased serum levels of TGF-β and increased numbers of FoxP3+ CD4+ T cells in lymph nodes. In vitro, the addition of SLPI significantly decreased the number of functional FoxP3+ CD25(hi) CD4+ regulatory T cells in cultures of naive human CD4+ T cells. Adding recombinant TGF-β to SLPI-treated human T cell cultures neutralized SLPI's inhibitory effect on regulatory T cell differentiation.
  
  
  CONCLUSIONS
  In EAE, SLPI exerts potent pro-inflammatory actions by modulation of T-cell activity and its neutralization may be beneficial for the disease.
authors.affiliation: Multiple Sclerosis Research Center of New York, 521 W 57th Street, 4th floor, New York, NY 10019, USA. amueller@msrcny.org
authors.forename: André Michael
authors.initials: AM
authors.lastname: Müller
authors.forename: Esther
authors.initials: E
authors.lastname: Jun
authors.forename: Hana
authors.initials: H
authors.lastname: Conlon
authors.forename: Saud Ahmed
authors.initials: SA
authors.lastname: Sadiq
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000494:pharmacology / Q000627:therapeutic use*; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D002478:Cells, Cultured; D018450:Disease Progression; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D005260:Female; D006801:Humans; D007249:Inflammation / Q000276:immunology / Q000378:metabolism; D051379:Mice; D051381:Rats; D053481:Secretory Leukocyte Peptidase Inhibitor / Q000037:antagonists & inhibitors* / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism
chemical_list: D057134:Antibodies, Neutralizing; D053481:Secretory Leukocyte Peptidase Inhibitor; C506815:Slpi protein, mouse; D016212:Transforming Growth Factor beta