title: Alteration of cytokine levels by fosfomycin and prednisolone in spontaneous proliferation of cultured lymphocytes from patients with HTLV-I-associated myelopathy (HAM/TSP).
abstract: 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.
authors.affiliation: The Third Department of Internal Medicine, Faculty of Medicine, Kagoshima University, Japan. yamano@med6.kufm.kagoshima-u.ac.jp
authors.forename: Y
authors.initials: Y
authors.lastname: Yamano
authors.forename: K
authors.initials: K
authors.lastname: Machigashira
authors.forename: S
authors.initials: S
authors.lastname: Ijichi
authors.forename: K
authors.initials: K
authors.lastname: Usuku
authors.forename: M
authors.initials: M
authors.lastname: Kawabata
authors.forename: K
authors.initials: K
authors.lastname: Arimura
authors.forename: M
authors.initials: M
authors.lastname: Osame
mesh_terms: D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002478:Cells, Cultured; D003470:Culture Media / Q000032:analysis; D016207:Cytokines / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005578:Fosfomycin / Q000494:pharmacology*; D006801:Humans; D008214:Lymphocytes / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D015493:Paraparesis, Tropical Spastic / Q000378:metabolism*; D011239:Prednisolone / Q000494:pharmacology*; D013936:Thymidine / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D000893:Anti-Inflammatory Agents; D003470:Culture Media; D016207:Cytokines; D005578:Fosfomycin; D011239:Prednisolone; D013936:Thymidine