title: Micro-encapsulated secretory leukocyte protease inhibitor decreases cell-mediated immune response in autoimmune orchitis.
abstract: OBJECTIVE
  We previously reported that recombinant human Secretory Leukocyte Protease Inhibitor (SLPI) inhibits mitogen-induced proliferation of human peripheral blood mononuclear cells. To determine the relevance of this effect in vivo, we investigated the immuno-regulatory role of SLPI in an experimental autoimmune orchitis (EAO) model.
  
  
  METHODS
  In order to increase SLPI half life, poly-ε-caprolactone microspheres containing SLPI were prepared and used for in vitro and in vivo experiments. Multifocal orchitis was induced in Sprague-Dawley adult rats by active immunization with testis homogenate and adjuvants. Microspheres containing SLPI (SLPI group) or vehicle (control group) were administered s.c. to rats during or after the immunization period.
  
  
  RESULTS
  In vitro SLPI-release microspheres inhibited rat lymphocyte proliferation and retained trypsin inhibitory activity. A significant decrease in EAO incidence was observed in the SLPI group (37.5%) versus the control group (93%). Also, SLPI treatment significantly reduced severity of the disease (mean EAO score: control, 6.33±0.81; SLPI, 2.72±1.05). In vivo delayed-type hypersensitivity and ex vivo proliferative response to testicular antigens were reduced by SLPI treatment compared to control group (p<0.05).
  
  
  CONCLUSIONS
  Our results highlight the in vivo immunosuppressive effect of released SLPI from microspheres which suggests its feasible therapeutic use.
authors.affiliation: Instituto de Investigaciones en Reproducción, Universidad de Buenos Aires, Argentina.
authors.forename: Vanesa Anabella
authors.initials: VA
authors.lastname: Guazzone
authors.forename: Diego
authors.initials: D
authors.lastname: Guerrieri
authors.forename: Patricia
authors.initials: P
authors.lastname: Jacobo
authors.forename: Romina Julieta
authors.initials: RJ
authors.lastname: Glisoni
authors.forename: Diego
authors.initials: D
authors.lastname: Chiappetta
authors.forename: Livia
authors.initials: L
authors.lastname: Lustig
authors.forename: H Eduardo
authors.initials: HE
authors.lastname: Chuluyan
mesh_terms: D000818:Animals; D001327:Autoimmune Diseases / Q000188:drug therapy* / Q000276:immunology; D049109:Cell Proliferation / Q000187:drug effects; D004195:Disease Models, Animal; D004339:Drug Compounding; D006968:Hypersensitivity, Delayed / Q000188:drug therapy; D007111:Immunity, Cellular / Q000187:drug effects* / Q000276:immunology; D007155:Immunologic Factors / Q000494:pharmacology*; D007165:Immunosuppression Therapy; D008214:Lymphocytes / Q000187:drug effects; D008297:Male; D008863:Microspheres; D009920:Orchitis / Q000188:drug therapy* / Q000276:immunology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins; D053481:Secretory Leukocyte Peptidase Inhibitor / Q000494:pharmacology*
chemical_list: D007155:Immunologic Factors; D011994:Recombinant Proteins; D053481:Secretory Leukocyte Peptidase Inhibitor