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-alpha (IFN-alpha) therapy was studied in seven patients with HTLV-I-associated myelopathy (HAM)/tropical spastic paraparesis (TSP). IFN-alpha was administered at a dose of 6 x 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-alpha. The other patient who responded to IFN-alpha 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-alpha in the responders who completed long-term IFN-alpha 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-alpha therapy contributed to its sustained clinical benefits.

• Authors: K Yamasaki, J Kira, Y Koyanagi, Y Kawano, N Miyano-Kurosaki, M Nakamura, E Baba, J Suzuki, A Yamamoto, N Yamamoto, T Kobayashi
• Journal: Journal of the neurological sciences (J Neurol Sci) Vol. 147 Issue 2 Pg. 135-44 (Apr 15 1997) ISSN: 0022-510X [Print] Netherlands
• PMID: 9106118 (Publication Type: Clinical Trial, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• DNA, Viral
• Interferon-alpha
• Receptors, Interleukin-2

Topics

• Adult
• Aged
• Cell Division (drug effects, immunology)
• DNA, Viral (analysis)
• Female
• Human T-lymphotropic virus 1 (genetics, immunology)
• Humans
• Interferon-alpha (administration & dosage)
• Lymphocyte Subsets (cytology, drug effects, immunology)
• Male
• Middle Aged
• Paraparesis, Tropical Spastic (drug therapy, immunology, virology)
• Pilot Projects
• Receptors, Interleukin-2 (blood, immunology)