Fosfomycin has recently been reported as an
antibiotic with immunomodulatory activities. To evaluate the possibility of clinical administration of
fosfomycin in patients with human T lymphotropic virus type I (
HTLV-I)-associated myelopathy/tropical spastic paraparesis (HAM/TSP), the effects of this agent on the HTLV-I-induced in vitro phenomenon were studied. The influence of
fosfomycin on in vitro spontaneous proliferation (SP) of peripheral blood mononuclear cells (PBMCs) from four patients with HAM/TSP was measured by
thymidine incorporation into the cells, and the concentration of several
cytokines in the culture supernatants was examined in three HAM/TSP patients.
Enzyme-linked
immunosorbent assays (ELISAs) were employed to detect the concentrations of
interleukin-4 (IL-4),
IL-6,
IL-10,
interferon-gamma (IFN-gamma),
transforming growth factor-beta1 (TGF-beta1), and macrophage inflammatory protein-1alpha (MIP-1alpha). The data were compared to the changes by
prednisolone which is known to regulate the HTLV-I-associated in vitro phenomenon and to have a therapeutic benefit in patients with HAM/TSP. Production of
IL-6, IFN-gamma and
MIP-1alpha from the spontaneously proliferating cells were demonstrated.
Fosfomycin could not suppress the HTLV-I-associated SP, but had the properties to decrease the levels of
TGF-beta1 and
MIP-1alpha. It was also demonstrated that the concentrations of IFN-gamma and
MIP-1alpha in the cultures in the presence of
prednisolone were apparently decreased, suggesting a possible involvement of these
cytokines in the pathogenesis of HAM/TSP. These findings support the hypothesis that
fosfomycin may have immunomodulatory potentials in HTLV-I-related cellular interactions in a different manner from ordinary
immunomodulatory agents.