The increase in intra-macrophage thiols induced by new pro-GSH molecules directs the Th1 skewing in ovalbumin immunized mice.
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, 2h-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.
Fraternale
Alessandra
A
Department of Biomolecular Sciences, University of Urbino "Carlo Bo", Via Saffi, 2, 61029 Urbino (PU), Italy. alessandra.fraternale@uniurb.it
Paoletti
Maria Filomena
MF
Dominici
Sabrina
S
Caputo
Antonella
A
Castaldello
Arianna
A
Millo
Enrico
E
Brocca-Cofano
Egidio
E
Smietana
Michaël
M
Clayette
Pascal
P
Oiry
Joël
J
Benatti
Umberto
U
Magnani
Mauro
M
D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000818:Animals; D000917:Antibody Formation; D002478:Cells, Cultured; D005260:Female; D005978:Glutathione / Q000276:immunology*; D007111:Immunity, Cellular; D007074:Immunoglobulin G / Q000097:blood; D017737:Macrophages, Peritoneal / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008813:Mice, Inbred ICR; D010047:Ovalbumin / Q000276:immunology; D010084:Oxidation-Reduction; D013438:Sulfhydryl Compounds / Q000032:analysis / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*
D000276:Adjuvants, Immunologic; D007074:Immunoglobulin G; D013438:Sulfhydryl Compounds; D010047:Ovalbumin; D005978:Glutathione