Fosfomycin, an antibiotic, possessed TGF-beta-like immunoregulatory activities.

The regulatory effects of fosfomycin (FOM) were correlated closely with the multifunction of TGF-beta 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-beta. Neither FOM nor TGF-beta 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-beta was partly overcome with soluble TFG-beta 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-beta. The addition of FOM and latent TGF-beta inhibited the proliferation of Mv1Lu cells, but FOM did not lead to an increase in plasmin activities, which convert latent to active TGF-beta, and further the expression of TGF-beta receptors on the cell surface. In addition, FOM failed to enhance TGF-beta secretion. These findings suggest that immunomodulation of FOM results in increased sensitivity of cells to TGF-beta.