Micro-encapsulated Secretory Leukocyte Protease Inhibitor decreases cell-mediated immune response in autoimmune orchitis

GUAZZONE, VA; GUERRIERI D; JACOBO, P; GLISONI, RJ; CHIAPPETTA, DIEGOAPPETTA; LUSTIG, L; CHULUYAN, HE

LIFE SCIENCES

PERGAMON-ELSEVIER SCIENCE LTD

Lugar: Oxford; Año: 2011 p. 100 - 106

0024-3205

Aims: We previously reported that recombinant human Secretory Leukocyte ProteaseInhibitor (SLPI) inhibits mitogen-induced proliferation of human peripheral bloodmononuclear cells. To determine the relevance of this effect in vivo, we investigated theimmunoregulatory role of SLPI in an experimental autoimmune orchitis (EAO) model.Main methods: In order to increase SLPI half life, poly-ε-caprolactone microspherescontaining SLPI were prepared and used for in vitro and in vivo experiments. Multifocalorchitis was induced in Sprague-Dawley adult rats by active immunization with testishomogenate and adjuvants. Microspheres containing SLPI (SLPI group) or vehicle (controlgroup) were administered s.c. to rats during or after the immunization period.Key findings: in vitro SLPI-release microspheres inhibited rat lymphocyte proliferation andretained trypsin inhibitory activity. A significant decrease in EAO incidence was observed inthe SLPI group (37.5%) versus the control group (93%). Also, SLPI treatment significantlyreduced 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 testicularantigens were reduced by SLPI treatment compared to control group (p<0.05).Significance: Our results highlight the in vivo immunosuppressive effect of released SLPIfrom microspheres suggesting its feasible therapeutic use.