Long term, high dose interferon-alpha treatment in HTLV-I-associated myelopathy/tropical spastic paraparesis: a combined clinical, virological and immunological study

Abstract

The efficacy of long-term, high dose interferon-α (IFN-α) therapy was studied in seven patients with HTLV-I-associated myelopathy (HAM)/tropical spastic paraparesis (TSP). IFN-α was administered at a dose of 6 × 10 6 international units daily for the initial 2 weeks and thereafter 3 times a week for the following 22 weeks. Five patients showed a sustained improvement in motor performance during and up to 6 months after the completion of IFN-α. The other patient who responded to IFN-α initially dropped out at 3 months because of depression, while another patient first deteriorated and thereafter dropped out. In the six responders, the absolute number of peripheral blood lymphocytes (PBL) harboring the HTLV-I genome as evaluated by the quantitative polymerase chain reaction method decreased significantly during the therapy period (28.6 ± 16.6% reduction, P = 0.0083), whereas the one deteriorated patient showed a 2.5-fold increase in HTLV-I-infected cells. The autoproliferation of CD4 + T clone cells from a single cell culture was markedly depressed even after the cessation of IFN-α in the responders who completed long-term IFN-α therapy. In addition, the CD8 +DR + T cells in the peripheral blood and soluble IL-2 receptor levels in the sera increased significantly during the therapy in all patients ( P = 0.0431 and P = 0.0041, respectively). Therefore, the results of our study suggested that both the reduction of HTLV-I proviral DNA load and immunomodulation by long-term IFN-α therapy contributed to its sustained clinical benefits.