Interferon-beta1a therapy in human T-lymphotropic virus type I-associated neurologic disease.
Human T-lymphotropic virus type I (HTLV-I)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is an immune-mediated inflammatory disorder of the central nervous system. Immune activation in the host, which results from high levels of persistent antigenic stimulation and from transactivation of host immunoregulatory genes by HTLV-I, appears important in the pathogenesis of HAM/TSP. In a single-center, open-label trial, 12 patients with HAM/TSP were treated with doses of interferon-beta1a of up to 60mug twice weekly, based on its antiviral and immunomodulatory effects. Primary end points were immunological and virological measures that are potential biomarkers for HAM/TSP. Interferon-beta1a therapy reduced the HTLV-I tax messenger RNA load and the frequency of potentially pathogenic HTLV-I-specific CD8(+) cells. The HTLV-I proviral DNA load remained unchanged. Spontaneous lymphoproliferation, a marker of T-cell activation in HAM/TSP, also was reduced. Some measures of motor function were improved, and no significant clinical progression occurred during therapy. These results indicate that interferon-beta1a may beneficially affect the immune mechanisms central to the pathogenesis of HAM/TSP.
Oh
Unsong
U
Neuroimmunology Branch, National Institute of Neurological Disorders and Stroke, Bethesda, MD, USA.
Yamano
Yoshihisa
Y
Mora
Carlos A
CA
Ohayon
Joan
J
Bagnato
Francesca
F
Butman
John A
JA
Dambrosia
James
J
Leist
Thomas P
TP
McFarland
Henry
H
Jacobson
Steven
S
D000328:Adult; D000368:Aged; D015415:Biomarkers; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000821:virology; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004279:DNA, Viral / Q000187:drug effects; D005260:Female; D005434:Flow Cytometry; D015368:Human T-lymphotropic virus 1 / Q000187:drug effects; D006801:Humans; D016899:Interferon-beta / Q000627:therapeutic use*; D008213:Lymphocyte Activation / Q000187:drug effects; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D015493:Paraparesis, Tropical Spastic / Q000188:drug therapy*; D011533:Proviruses / Q000187:drug effects; D020127:Recovery of Function / Q000187:drug effects
D015415:Biomarkers; D004279:DNA, Viral; D016899:Interferon-beta