Micro-encapsulated secretory leukocyte protease inhibitor decreases cell-mediated immune response in autoimmune orchitis

LIFE SCIENCES

卷:89

Article

Guazzone, Vanesa Anabella²  Jacobo, Patricia²  Glisoni, Romina Julieta³  Chiappetta, Diego³  Lustig, Livia²  Chuluyan, H. Eduardo¹ 

[1] Univ Buenos Aires, Fac Med, Catedra Farmacol 3ra, Dept Farmacol, RA-1121 Buenos Aires, DF, Argentina

[2] Univ Buenos Aires, Fac Med, Inst Invest Reprod, RA-1121 Buenos Aires, DF, Argentina

[3] Univ Buenos Aires, CONICET, Fac Farm & Bioquim, Dept Tecnol Farmaceut, RA-1121 Buenos Aires, DF, Argentina

关键词: Autoimmune orchitis;    Secretory leukocyte protease inhibitor;    Drug delivery systems;    Immuno-modulation;    Delayed type hypersensitivity;   

DOI  :  10.1016/j.lfs.2011.05.002

来源: Elsevier

【 摘 要 】

Aims: 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. Main methods: In order to increase SLPI half life, poly-epsilon-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 (SUN group) or vehicle (control group) were administered s.c. to rats during or after the immunization period. Key findings: 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). Significance: Our results highlight the in vivo immunosuppressive effect of released SLPI from microspheres which suggests its feasible therapeutic use. (C) 2011 Elsevier Inc. All rights reserved.

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