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) 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.
Yamasaki
K
K
Department of Neurology, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Kira
J
J
Koyanagi
Y
Y
Kawano
Y
Y
Miyano-Kurosaki
N
N
Nakamura
M
M
Baba
E
E
Suzuki
J
J
Yamamoto
A
A
Yamamoto
N
N
Kobayashi
T
T
D000328:Adult; D000368:Aged; D002455:Cell Division / Q000187:drug effects / Q000276:immunology; D004279:DNA, Viral / Q000032:analysis; D005260:Female; D015368:Human T-lymphotropic virus 1 / Q000235:genetics / Q000276:immunology; D006801:Humans; D016898:Interferon-alpha / Q000008:administration & dosage*; D016131:Lymphocyte Subsets / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D008297:Male; D008875:Middle Aged; D015493:Paraparesis, Tropical Spastic / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D010865:Pilot Projects; D015375:Receptors, Interleukin-2 / Q000097:blood / Q000276:immunology
D004279:DNA, Viral; D016898:Interferon-alpha; D015375:Receptors, Interleukin-2