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: Y Yamano, K Machigashira, S Ijichi, K Usuku, M Kawabata, K Arimura, M Osame
• Journal: Journal of the neurological sciences (J Neurol Sci) Vol. 151 Issue 2 Pg. 163-7 (Oct 22 1997) ISSN: 0022-510X [Print] Netherlands
• PMID: 9349671 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Bacterial Agents
• Anti-Inflammatory Agents
• Culture Media
• Cytokines
• Fosfomycin
• Prednisolone
• Thymidine

Topics

• Adult
• Aged
• Anti-Bacterial Agents (pharmacology)
• Anti-Inflammatory Agents (pharmacology)
• Cells, Cultured
• Culture Media (analysis)
• Cytokines (metabolism)
• Enzyme-Linked Immunosorbent Assay
• Female
• Fosfomycin (pharmacology)
• Humans
• Lymphocytes (drug effects, metabolism)
• Male
• Middle Aged
• Paraparesis, Tropical Spastic (metabolism)
• Prednisolone (pharmacology)
• Thymidine (metabolism)