The increase in intra-macrophage thiols induced by new pro-GSH molecules directs the Th1 skewing in ovalbumin immunized mice

• Published in: Vaccine 2010-11, Vol.28 (48), p.7676-7682
• Main Authors: Fraternale, Alessandra, Paoletti, Maria Filomena, Dominici, Sabrina, Caputo, Antonella, Castaldello, Arianna, Millo, Enrico, Brocca-Cofano, Egidio, Smietana, Michaël, Clayette, Pascal, Oiry, Joël, Benatti, Umberto, Magnani, Mauro
• Format: Article
• Language: English
• Subjects: Adjuvants, Immunologic - pharmacology; Allergy and Immunology; Animals; Antibody Formation; Applied microbiology; Bacterial infections; Biological and medical sciences; Cells, Cultured; Cytokines; Female; Fundamental and applied biological sciences. Psychology; Glutathione - immunology; Immune response; Immunity, Cellular; Immunization; Immunoglobulin G - blood; Laboratory animals; Macrophage redox state; Macrophages, Peritoneal - immunology; Macrophages, Peritoneal - metabolism; Mice; Mice, Inbred C57BL; Mice, Inbred ICR; Microbiology; Ovalbumin - immunology; Oxidation-Reduction; Pro-GSH molecules; Studies; Sulfhydryl Compounds - analysis; Sulfhydryl Compounds - immunology; Th1/Th2 responses; Th2 Cells - immunology; Vaccines; Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies (general aspects); Viral infections
• ISSN: 0264-410X; 1873-2518
• DOI: 10.1016/j.vaccine.2010.09.033

Abstract In the present work, the capacity of new pro-GSH molecules to increase the intra-macrophage thiol content in vitro and in vivo as well as to shift the immune response to Th1 in ovalbumin (Ova)-sensitized mice were examined. The molecules were the N-butanoyl GSH derivative, GSH-C4, and a pro-drug of N-acetylcysteine (NAC) and beta-mercaptoethylamine (MEA), I-152. In vitro, 2 h-incubation with both molecules was found to increase intra-macrophage thiol content; in vivo, Ova-sensitized mice pre-treated by intraperitoneal administration of the pro-GSH molecules showed an increase in plasma anti-Ova IgG2a and IgG2b, characterizing Th1 immune response, and a decrease in IgG1, typical of the Th2 response. Such findings were connected to a shift to a Th1 response also involving splenocyte IFN-γ production as revealed by ELISPOT assay and higher levels of IL-12 in circulation. Although immune responses are in vivo mediated both by dendritic cells and macrophages, the data reported in this paper corroborate the suggestion that the pro-GSH molecules, increasing the intra-cellular thiol pool, modulate the Th1/Th2 balance favouring Th1-type responses and may be employed as Th1-directing adjuvants in new vaccination protocols and as immunomodulators in those diseases where Th1 response patterns are compromised in favour of Th2.