Further analysis of the use of Toxoplasma gondii serine proteasae inhibitor-1 for the treatment of allergic lung inflammation.

SOTO ARIADNA, FENOY IGNACIO, SANCHEZ VANESA, MARCH FLORENCIA, PICCHIO MARIANO, ALDIRICO MARIA DE LOS ÁNGELES, PERRONE SIBILIA MATÍAS, DRAN GRACIELA, MARTÍN VALENTINA, GOLDMAN ALEJANDRA.

Congreso; LXII Reunión Anual de la Sociedad Argentina de Inmunología; 2014

By using a murine allergic airway inflammation model, we had previously shown that Toxoplasma gondii serin-proteases inhibitor 1 (PI) was able to reduce BAL eosinophilia and lung mucus production. Herein, we extended our study by analysing the immune mechanisms involved. BALB/c mice were ip sensitized with OVA (allergen) /Alum and aerosol challenged with OVA. Two days later they were intranasally (IN) treated for 3 days with OVA + PI (OPI). Control groups included non-sensitized mice IN treated with PI alone (NPI) (negative) and sensitized mice treated with OVA alone (OO) (positive). One week later, mice were OVA aerosol challenged. PI treated mice showed a decrease in OVA specific IgG1 and IgG2a (IgG1: NPIª: 0,01±0,002; OOb: 0,13±0,01; OPIc: 0,09±0,01; OD±ES p<0,01 b vs c; IgG2a: NPIª: 0,04±0,005; OOb: 1,53±0,22; OPIc: 0,55±0,05; OD±ES p<0,01 b vs c). Also, a trend to decreased IgE levels was observed. IL-4, IL-5 and IFN-γ production was reduced in thoracic lymph node cells from PI treated mice ex vivo stimulated with OVA (IL-4: NPIa: 5,3±0,16; OOb: 1442±203,7; OPIc: 680,9±159,7 pg/ml±ES, p<0,01 b vs c; IL-5: NPIa: 5,0±8,0; OOb: 4794±298,9; OPIc: 1664±345,8 pg/ml±ES; p<0,001 b vs c; IFN-γ: NPIa: 0,017±0,0; OOb: 1,326 2±0,56; OPIc: 0,265±0,08 OD±ES, p<0,05 b vs c). Regulatory cytokines were also diminished (IL-10: NPIa: 53,42±2,2; OOb: 4507±1266; OPIc: 1682±289,3 pg/ml±ES, p<0,05 b vs c; TGF-β: NPI: 1424±285,1; OOb: 15402±450,3; OPIc: 647,5±66,83 pg/ml±ES; p<0,05 b vs c). Moreover, PI induced a reduction in OVA specific T cell proliferation (OO: 23907±2577; OPI: 12285±2103 ∆cpm ± ES, p <0.05). This model shows the potential use of PI in respiratory immunotherapies. The results suggest that the effect of PI in modulating allergic lung inflammation would be the result of a decrease in the overall response to the allergen.