LONG-TERM, HIGH-DOSE INTERFERON-ALPHA TREATMENT IN HTLV-I-ASSOCIATED MYELOPATHY TROPICAL SPASTIC PARAPARESIS - A COMBINED CLINICAL, VIROLOGICAL AND IMMUNOLOGICAL STUDY/

The efficacy of long-term, high dose interferon-alpha (IFN-alpha) ther apy was studied in seven patients with HTLV-I-associated myelopathy (H AM)/tropical spastic paraparesis (TSP). IFN-alpha was administered at a dose of 6x10(6) international units daily for the initial 2 weeks an d 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-alpha. The other patient who respo nded to IFN-alpha initially dropped out at 3 months because of depress ion, while another patient first deteriorated and thereafter dropped o ut. In the six responders, the absolute number of peripheral blood lym phocytes (PBL) harboring the HTLV-I genome as evaluated by the quantit ative 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 ce lls. The autoproliferation of CD4(+) T clone cells from a single cell culture was markedly depressed even after the cessation of IFN-alpha i n the responders who completed long-term IFN-alpha therapy. In additio n, the CD8(+)DR(+) T cells in the peripheral blood and soluble IL-2 re ceptor levels in the sera increased significantly during the therapy i n all patients (P=0.0431 and P=0.0041, respectively). Therefore, the r esults of our study suggested that both the reduction of HTLV-I provir al DNA load and immunomodulation by long-term IFN-alpha therapy contri buted to its sustained clinical benefits. (C) 1997 Elsevier Science B. V.