Fosfomycin, an antibiotic, possessed TGF- β-like immunoregulatory activities

Abstract

The regulatory effects of fosfomycin (FOM) were correlated closely with the multifunction of TGF-β in the modulation of immune responses in vivo and in vitro. LPS-induced polyclonal IgM and IgG antibody responses were depressed at 3 days after the initial culture and subsequently enhanced at day 10 by FOM or TGF-β. Neither FOM nor TGF-β inhibited LPS-induced IgA antibody responses, whereas dexamethasone (DX) reduced polyclonal IgM, IgG and IgA antibody responses wholly. The suppression of antibody responses and Mv1Lu cell proliferation induced by FOM or TGF-β was partly overcome with soluble TFG-β receptors (sRIII). Oral, i.v. and i.p. administration of FOM exhibited similar enhanced SRBC-specific antibody responses to that seen after oral administration of TGF-β. The addition of FOM and latent TGF-β inhibited the proliferation of Mv1Lu cells, but FOM did not lead to an increase in plasmin activities, which convert latent to active TGF-β, and further the expression of TGF-β receptors on the cell surface. In addition, FOM failed to enhance TGF-β secretion. These findings suggest that immunomodulation of FOM results in increased sensitivity of cells to TGF-β.