[Immunopathogenesis and treatment of the myelopathy associated to the HTLV-I virus].
BACKGROUND
Human T-cell lymphotropic virus type-I (HTLV-I) causes tropical spastic paraparesis/HTLV-I associated myelopathy (TSP/HAM). Immunopathogenesis and available treatments for TSP/HAM are reviewed.


METHODS
At least 20 million people are infected worldwide and 0.3-4% will develop TSP/HAM. Incidence in endemic areas is around 2 cases/ 100,000 inhabitants and year. The 50% of TSP/HAM patients suffer from clinical progression during their first ten years. Progression is associated with high proviral load and ager than 50 years at onset. HTLV-I proviral DNA and m-RNA load are significantly raised in TSP/HAM patients compared to asymptomatic carriers. This antigenic load activates T cells CD8+ specific for Tax-protein, which up-regulate pro-inflammatory cytokines. Corticoids, plasma-exchange, intravenous immunoglobulins, danazol, pentoxifilline, green-tea polyphenols, lactobacillus fermented milk, zidovudine, lamivudine, monoclonal antibodies (daclizumab), interferon, and valproic acid have been used in open trials in a small number of patients. Nevertheless, their clinical efficacy is limited. Interferon alpha and beta-1a have cytostatic properties and may cause a reduction in HTLV-I proviral load.


CONCLUSIONS
High HTLV-I proviral load and an exaggerated pro-inflammatory cellular response are involved in the pathogenesis of TSP/HAM. No therapy has been conclusively shown to alter long-term disability associated with TSP/HAM. Multicentric clinical trials are necessary to assess long-term efficacy of interferon in TSP/HAM.
Carod-Artal
F J
FJ
Servicio de Neurología,Hospital Sarah, Red Sarah de Hospitales de Rehabilitacion, Brasilia DF, Brazil. javier@sarah.br
D000305:Adrenal Cortex Hormones / Q000627:therapeutic use; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000627:therapeutic use; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D003937:Diagnosis, Differential; D018450:Disease Progression; D015490:HTLV-I Infections / Q000453:epidemiology / Q000276:immunology* / Q000473:pathology* / Q000503:physiopathology; D015368:Human T-lymphotropic virus 1 / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology / Q000627:therapeutic use; D015493:Paraparesis, Tropical Spastic / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology / Q000821:virology*; D013118:Spinal Cord Diseases / Q000188:drug therapy* / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology; D019562:Viral Load
D000305:Adrenal Cortex Hormones; D000911:Antibodies, Monoclonal; D007371:Interferon-gamma