CONICET | Buscador de Institutos y Recursos Humanos

EVIDENCES OF APOPTOSIS AND CYTOKINE LEVELS REGULATION IN COLLAGEN-INDUCED ARTHRITIS BY PLACENTAL-DERIVED PROTEINS M.M. Cortes 1, A. Canellada 1, T. Gentile 1 1 Catedra De Inmunologia, Facultad De Farmacia Y Bioquimica, Universidad De Buenos Aires, Buenos Aires, Argentina We have previously found that placental factors (PF) and the 12-24 kDa PF-derived fraction treatment reduced the severity of collagen induced arthritis (CIA) in rats, strongly diminished serum anti collagen type II (CII) antibodies and affected differentially IgG1/IgG2a ratio. In order to evaluate other immunoregulatory mechanisms of placental derived proteins on arthritis remission, we assessed the in vitro effect of PF and the 12-24kDa derived fraction (not yet characterized) on self-reactive cells apoptosis and IFNã (Th1) and IL-10 (Th2) levels.Rats with CIA (n=10) were scored for arthritis. Spleen cells were incubated with and without PF (20%) or 12-24kDa placenta- derived protein (1µg) in presence or absence of CII.IFNã and IL-10 levels were determined by ELISA. Apoptosis in spleen cells was analyzed by detecting Annexin-V (FITC conjugated) and propidium iodide positive cells using flow cytometry.In vitro addition of PF increased apoptotic rates on spleen cells, reduced the levels of IFNã by a 70% (p<0.01 vs controls) and increased the IL-10 level (3 fold p<0.001 vs controls) secreted by antigen-activated spleen cells from CIA females. On the other hand, the 12-24 kDa placenta-derived protein was able to increase the susceptibility of CIA spleen cells to antigen (CII) induced apoptosis.Taken together these results indicate a shift from Th1 towards Th2 response and the inhibition of Th1-proimmflamatory cells by apoptosis of activated cells. Our observations suggest that placenta-derived factors may be at least partially responsible for pregnancy-associated suppression of arthritogenic process in CIA rats.