Micro-encapsulated secretory leukocyte protease inhibitor reduces incidence and severity of autoimmune orchitis in rats

GUAZZONE V.; GUERRIERI D.; JACOBO P.; GLISONI R.J.; CHIAPPETTA D.A.; LUSTIG L.; CHULUYAN H.E.

Chile

Congreso; 9th Latin American Congress of Immunology.; 2009

Latin American Association of Immunology (ALAI).

Secretory leukocyte protease inhibitor (SLPI) has numerous functions not related to its protease-inhibitory activity. We previously described that recombinant human SLPI (rhSLPI) inhibits human peripheral blood mononuclear cells mitogen-induced proliferation. To determine the relevance of this effect in vivo, we investigated the immunoregulatory role of SLPI in an experimental autoimmune orchitis (EAO) model useful to study chronic testicular inflammation. Poly-å-caprolactone microspheres containing rhSLPI were prepared in order to increase the SLPI half life. In vitro rhSLPI was able to inhibit rat lymphocyte proliferation retaining the trypsin inhibitory activity after microsphere release. A multifocal orchitis was induced in Sprague-Dawley adult rats by active immunization with testis homogenate and adjuvants. Microspheres containing rhSLPI (rhSLPI group) or vehicle (control group) were administrated to rats after the immunization period. A significant decrease in EAO incidence was observed in rhSLPI group (37.5%) versus control group (93%). Also, rhSLPI treatment significantly ameliorated the disease severity (mean EAO score: control, 6.33 ± 0.81; rhSLPI, 2.72 ± 1.05). In vivo delayed-type hypersensitivity and in vitro proliferative response to testicular antigens were reduced by rhSLPI treatment compared with control group (p