ALTERATION OF CYTOKINE LEVELS BY FOSFOMYCIN AND PREDNISOLONE IN SPONTANEOUS PROLIFERATION OF CULTURED LYMPHOCYTES FROM PATIENTS WITH HTLV-I-ASSOCIATED MYELOPATHY (HAM TSP)/

Fosfomycin has recently been reported as an antibiotic with immunomodu latory activities. To evaluate the possibility of clinical administrat ion 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 we re studied. The influence of fosfomycin on in vitro spontaneous prolif eration (SP) of peripheral blood mononuclear cells (PBMCs) from four p atients with HAM/TSP was measured by thymidine incorporation into the cells, and the concentration of several cytokines in the culture super natants was examined in three HAM/TSP patients. Enzyme-linked immunoso rbent assays (ELISAs) were employed to detect the concentrations of in terleukin-4 (IL-4), IL-6, IL-10, interferon-gamma (IFN-gamma), transfo rming growth factor-beta 1 (TGF-beta 1), and macrophage inflammatory p rotein-1 alpha (MIP-1 alpha). The data were compared to the changes by prednisolone which is known to regulate the HTLV-I-associated in vitr o phenomenon and to have a therapeutic benefit in patients with HAM/TS P. Production of IL-6, IFN-gamma and MIP-1 alpha from the spontaneousl y proliferating cells were demonstrated. Fosfomycin could not suppress the HTLV-I-associated SP, but had the properties to decrease the leve ls of TGF-beta 1 and MIP-la. It was also demonstrated that the concent rations of IFN-gamma and MIP-1 alpha in the cultures in the presence o f prednisolone were apparently decreased, suggesting a possible involv ement of these cytokines in the pathogenesis of HAM/TSP. These finding s support the hypothesis that fosfomycin may have immunomodulatory pot entials in HTLV-I-related cellular interactions in a different manner from ordinary immunomodulatory agents. (C) 1997 Elsevier Science B.V.