Analysis of the molecular mechanisms of the development of HAM from the point of view of Th1/Th2 balance

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We investigated the molecular mechanisms of the development of HTLV-I associated myelopathy (HAM) from the point of view of Th1/Th2 balance in peripheral blood CD4+ T lymphocytes. Research results are as follows: 1) Elevated levels of interferon-γ (IFN-γ) in the sera and CSF based on elevated levels of serum IL-12 in HAM patients (J Neuroimmunol 95:185-189, 1999). 2) The fact of 1) was supported by clinical efficacy of pentoxifylline, which make up-regulation of Th2 cytokines, in treatment of HAM patients (Intern Med 38:717-721, 1999). 3) Increase of E-selectin+CD4ィイD1+ィエD1 T lymphocytes based on HTLV-I infection, which activities of IFN-γ expression are exaggerated, in peripheral blood T lymphocytes (PBT) of HAM patients (manuscript, submitted). 4) Increased Fas-madiated cytotoxicity of CD4ィイD1+ィエD1 T lymphocytes in HAM patients (J Neuroimmunol 86:198-201, 1998). 5) CD4ィイD1+ィエD1 T lymphocytes in HAM patients itself are resistant against apoptosis, under high expression of Bcl-xL which is one of anti-apoptotic protein in Fas/Fas ligand system (manuscript, submitted). 6) Matrix metalloproteinase-2 induction through VCAM-1/VLA-4 pathway is up-regulated in PBT of HAM patients (J Neuroimmunol 99:242-247, 1999). These results strongly suggest that the immunological balance of helper T lymphocytes between Th1 and Th2 is toward Th1 in the peripheral blood of HAM patients and Th1-mediated immunological status is involved in the development of HAM. In addition, the therapeutic approaches towards the correction of Th1/Th2 balance, such as pentoxifylline, might contribute to successful treatments against HAM patients.