Proviral load and the balance of serum cytocines in HTLV-1-asymptomatic infection and in HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) |
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| Affiliation: | 1. Programa de Pós-Graduação em Infectologia e Medicina Tropical - Faculdade de Medicina da Universidade Federal de Minas Gerais, Minas Gerais, Av. Prof. Alfredo Balena, 190 – sala 533, CEP: 30.130-100, Belo Horizonte, Minas Gerais, Brazil;2. Centro de Pesquisas René Rachou - FIOCRUZ-Minas, Av Augusto de Lima 1715 Barro Preto CEP: 30.190-002 Belo Horizonte, Minas Gerais, Brazil;3. Fundação Centro de Hematologia e Hemoterapia de Minas Gerais–HEMOMINAS, Rua Grão Pará, 882 -Santa Efigênia, CEP: 30130-110, Minas Gerais, Brazil;4. Hospital Sarah Kubitschek, Av. Amazonas, 5953 Gameleira, CEP: 30.510-000 Belo Horizonte, Minas Gerais, Brazil;5. Faculdade da Saúde e Ecologia Humana-FASEH, Rua São Paulo, 958 -Jardim Alterosa, CEP:33200-000 Vespasiano, Minas Gerais, Brazil;1. Department of Biotechnology, Manipal Life Sciences Centre, Manipal University, Manipal, Karnataka, India;2. Department of Medicine, Kasturba Hospital, Manipal University, Manipal, Karnataka, India;3. Department of Medicine, Kasturba Medical College, Manipal University, Mangalore, Karnataka, India;4. Department of Pathology, Kasturba Medical College, Manipal University, Mangalore, Karnataka, India;5. Department of Pathology, District Hospital, Udupi, Karnataka, India;1. Hematology & Oncology, Department of Internal Medicine, Iwate Medical University School of Medicine, Morioka, Iwate 020-8505, Japan;2. Department of Medical Oncology, Iwate Medical University School of Medicine, Morioka, Iwate 020-8505, Japan;1. Department of Epidemiology and Public Health, Swiss Tropical and Public Health Institute, P.O. Box, CH-4002 Basel, Switzerland;2. University of Basel, P.O. Box, CH-4003 Basel, Switzerland;3. Clinical Research & Epidemiology Section, Bernhard Nocht Institute for Tropical Medicine, Bernhard-Nocht-Str. 74, D-20359 Hamburg, Germany;4. DBL, Department of Veterinary Disease Biology, University of Copenhagen, Thorvaldsensvej 57, DK-1871 Frederiksberg C, Denmark;5. School of Biological & Conservation Sciences, Faculty of Science and Agriculture, University of KwaZulu-Natal, South Africa;1. Laboratório de Biodiversidade Entomológica, Instituto Oswaldo Cruz-Fiocruz, Rio de Janeiro, Brazil;2. Departamento de Ciências Biológicas, Faculdade de Ciências Farmacêuticas, UNESP, Araraquara, Brazil;3. Departament of Fisheries and Wildlife Sciences, University of Idaho, Moscow, USA;4. Laboratório de Eco-epidemiologia em Doença de Chagas, Instituto Oswaldo Cruz-Fiocruz, Brazil;1. Department of Medical Oncology and Immunology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan;2. Department of Hematology and Oncology, Graduate School of Medicine, Kyoto University, Kyoto, Japan;3. Department of Medicine and Biosystemic Science, Kyushu University, Fukuoka, Japan;4. Department of Blood Transfusion and Cellular Therapy, National Cancer Center Hospital, Tokyo, Japan;5. Division of Hematopoietic Stem Cell Transplantation, National Cancer Center Hospital, Tokyo, Japan;6. Department of Hematology, Imamura Bun-in Hospital, Kagoshima, Japan;7. Department of Hematology, Hamanomachi Hospital, Fukuoka, Japan;8. Department of Hematology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan;9. Department of Hematology, National Hospital Organization Kumamoto Medical Center, Kumamoto, Japan;10. Department of Hematology, National Kyushu Cancer Center, Fukuoka, Japan;11. Department of Hematology, Osaka Red Cross Hospital, Osaka, Japan;12. Tokyo Metropolitan Cancer and Infectious Disease Center, Komagome Hospital, Tokyo, Japan;13. Division of Epidemiology and Prevention, Aichi Cancer Center Research Institute, Nagoya, Japan;14. Department of Hematopoietic Stem Cell Transplantation Data Management/Biostatistics, Nagoya University, Nagoya, Japan |
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| Abstract: | This study compared the proviral load and the plasma cytokine profiles (interleukin-IL-2, IL-4, IL-6, IL-10, TNF-α, IFN-γ) in 87 HTLV-1-infected individuals, including 28 with HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), 32 with possible pHAM/TSP and 27 asymptomatic carriers (AC). The control group was composed by 21 HTLV-1-seronegative individuals. Our finding demonstrated that HAM/TSP group presented higher proviral load as compared to all other HTLV-1 groups (p < 0.0001). The HAM/TSP group showed higher serum concentration of IL-6 (p = 0.0009) as compared to all other groups. Moreover, higher serum concentration of IFN-γ (p = 0.0118) and IL-4 (p = 0.0166) were observed in HAM/TSP group as compared to the healthy controls. Additionally, the HAM/TSP group also showed higher serum concentration of TNF-α (p = 0.0239) and IFN-γ (p = 0.0118) as compared to AC. No differences in the serum concentration of IL-2 and IL-10 were observed among the groups. The analysis of cytokine balance demonstrated that HAM/TSP presented higher pro-inflammatory profile with enhanced IFN-γ/IL-10 and IFN-γ/IL-4 ratio as compared to AC and pHAM/TSP. Further analysis pointed out to a positive correlation between the IFN-γ response and the proviral load in AC. Conversely, a negative association between TNF-α and IL-2 with the proviral load was the hallmark of HAM/TSP group. These findings suggested that the proviral load and the pro-inflammatory cytokine profile may be independent events in the peripheral blood of HAM/TSP individuals. The knowledge about the existence of individual virological/immunological behavior upon HTLV-1 infection, may guide to the establishment of more effective therapeutic interventions. |
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