Análise do líquido cefalorraqueano e neuropatogênese da infecção pelo HTLV-I

Puccioni-Sohler, Marzia

doi:10.1590/S0004-282X1997000100024

Resumos

O mecanismo da mielopatia associada a infecção pelo HTLV-I (HAM), como ocorre o dano da medula espinhal e finalmente a destruição da mielina assim como do oligodendrócito não está definido. Por hipótese, a passagem de linfócitos infectados através da barreira hemato-encefálica atuaria como pedra alvo na patogênese da HAM. Um aumento da produção de citoquinas tais como o fator de necrose tumoral alfa (TNF alfa), potente imunomodulador, facilita a migração de linfócitos através da expressão de fatores de adesão molecular na superfície de células endoteliais. Por outro lado, a recente demonstração da elevada síntese intratecal do receptor solúvel para o TNF (sTNF-R) em pacientes com HAM tem contribuído para a melhor compreensão dos mecanismos da neuropatogênese da infecção pelo HTLV-I. Os novos conhecimentos sugerem que os efeitos deletérios do TNF alfa no sistema nervoso central podem ser o resultado do desequilíbrio entre a produção desta citoquina e do seu receptor inibidor (sTNF-R).

retovírus HTLV-I; líquido cefalorraqueano; sistema nervoso central; mielopatia; citoquinas; sTNF-R

The immunopathogenesis of the HTLV-I associated myelopathy (HAM) may be studied by the CSF evaluation. The mechanism of this myelopathy remains unknown. The disturbs of the cellular and humoral immune response observed in HAM patients suggest that the immunological derangement may contribute to the disease mechanisms. For hypothesis, the migration of infected lymphocytes through the blood-brain barrier could have a main role at the pathogenesis of HAM. An increase of the production of cytokines as tumor necrosis factor alpha (TNF alpha) contributes to the migration of lymphocytes through the expression of the intercellular adhesion molecule on the surface of the endothelial cells. On the other side, new knowledges suggest that the imbalance between the production of TNF alpha and its soluble receptor (sTNF-R) could result in the lesive effects of this cytokine in the central nervous system.

HTLV-I retrovirus; cerebrospinal fluid; central nervous system; myelopathy; cytokines; sTNF-R

Marzia Puccioni-Sohler

Neurologista, PhD, Serviço de Neurologia (Chefe: Prof. Dr. Sérgio Novis), Hospital Universitário Clementino Fraga Filho, Universidade Federal do Rio de Janeiro

RESUMO

O mecanismo da mielopatia associada a infecção pelo HTLV-I (HAM), como ocorre o dano da medula espinhal e finalmente a destruição da mielina assim como do oligodendrócito não está definido. Por hipótese, a passagem de linfócitos infectados através da barreira hemato-encefálica atuaria como pedra alvo na patogênese da HAM. Um aumento da produção de citoquinas tais como o fator de necrose tumoral alfa (TNF alfa), potente imunomodulador, facilita a migração de linfócitos através da expressão de fatores de adesão molecular na superfície de células endoteliais. Por outro lado, a recente demonstração da elevada síntese intratecal do receptor solúvel para o TNF (sTNF-R) em pacientes com HAM tem contribuído para a melhor compreensão dos mecanismos da neuropatogênese da infecção pelo HTLV-I. Os novos conhecimentos sugerem que os efeitos deletérios do TNF alfa no sistema nervoso central podem ser o resultado do desequilíbrio entre a produção desta citoquina e do seu receptor inibidor (sTNF-R).

Palavras-chave: retovírus HTLV-I, líquido cefalorraqueano, sistema nervoso central, mielopatia, citoquinas, sTNF-R.

ABSTRACT

The immunopathogenesis of the HTLV-I associated myelopathy (HAM) may be studied by the CSF evaluation. The mechanism of this myelopathy remains unknown. The disturbs of the cellular and humoral immune response observed in HAM patients suggest that the immunological derangement may contribute to the disease mechanisms. For hypothesis, the migration of infected lymphocytes through the blood-brain barrier could have a main role at the pathogenesis of HAM. An increase of the production of cytokines as tumor necrosis factor alpha (TNF alpha) contributes to the migration of lymphocytes through the expression of the intercellular adhesion molecule on the surface of the endothelial cells. On the other side, new knowledges suggest that the imbalance between the production of TNF alpha and its soluble receptor (sTNF-R) could result in the lesive effects of this cytokine in the central nervous system.

Key-words: HTLV-I retrovirus, cerebrospinal fluid, central nervous system, myelopathy, cytokines, sTNF-R.

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Aceite: 24-outubro-1996.

Dra. Marzia Puccioni-Sohler - Rua Dezenove de Fevereiro 185/ 705 - 22280-030 Rio de Janeiro RJ - Brasil. Fax: 021 295 1903.

1. Aderka D, Engelmann H, Shemer-Avni Y et al. Variation in serum levels of the soluble TNF receptors among healthy individuals. Lymphokine Cytokine Res1992; II: 157-159.
2. Aderka D, Wysenbeek A, Engelmann H et al. Correlation between serum levels of soluble tumor necrosis factor receptor and disease activity in systemic lupus erythematosus. Arth Rheumat 1993;36:1111-1120.
3. Cavalcanti M, Ferreira O, Puccioni M, No vis S, Schechter M. HTLV-I associated neurologic manifestations in four generations of a Brazilian family. J AIDS 1993;6:213-217.
4. Ceroni M, Picardo P, Rodgers- Johnson P et al. Intrathecal synthesis of IgG antibodies to HTLV-I supports an etiological role for HTLV-I in tropical spastic paraparesis. Ann Neurol 1988,23 (Suppl):S188-S191.
5. Chang Y, Allbright S, Lee F. Cytokines in the central nervous system: expression of macrophage colony stimulating factor and its receptor during development. J Neuroimmunol 1994;52:9-17.
6. Doukas J, Pober JS. IFN-gamma enhances endothelial activation induced by tumor necrosis factor but not IL-1. J Immunol 1990;145:1727-1733.
7. Gessain A, Caudie C, Gout O et al. Intrathecal synthesis of antibodies to human T lymphotropic virus type I and the presence of IgG oligogoclonal bands in the cerebrospinal fluid of patients with endemic tropical spastic paraparesis. J Infect Dis 1988;157:1226-1234.
8. Girardin E, Roux-Lombard P, Grau GE, Suter P, Gallati H. Imbalalance between rumour necrosis factor-alpha and soluble TNF receptor concentrations in severe meningococcaemia. Immunology 1992;76:20-23.
9. Godfried MH, van-der-Poll T, Jansen J et al. Soluble receptors for tumor necrosis factor: a putative marker of disease progression in HIV infection. AIDS 1993,7:33-36.
10. Grimaldi LM, Roos RP, Devare SG et al. HTLV-I associated myelopathy: oligoclonal immunoglobulin G bands contain anti-HTLV-I p24 antibody. Ann Neurol 1988,24:727-731.
11. Hõllsberg P, Hafler DA. Pathogenesis of diseases induced by human lymphotropic virus type I infection. N Engl J Med 1993;328:1173-1182.
12. Hughes CCW, Male DK, Lantos PL. Adhesion of lymphocytes to cerebral microvascular cells: effects of interferon-gamma, tumor necrosis factor and interleukin-1. Immunology 1988;64:677-681.
13. Kira J -I, Itoyama Y, Koyanagi Y et al. Presence of HTLV-I proviral DNA in central nervous system of patients with HTLV-I associated myelopathy. Ann Neurol 1992,31:39-45.
14. Mohler KM, Torrance DS, Smith Ca et al. Soluble tumor necrosis factor receptors are effective therapeutic agents in lethal endothoxemia and function simultaneously as both TNF carriers and TNF antagonists. J Immunol 1993; 151:1548-1561.
15. Nagasato K, NakamuraT, Ohishi K et al. Active production of anti-human T-lymphotropic virus type I (HTLV-I) IgM antibody in HTLV-I associated myelopathy. J Neuroimmunol 1991 ;32:105-109.
16. Nakamura S, Nagano I, Yoshioka M, Shimazaki S, Onodera J, Kogure K. Detection of tumor necrosis factor-a-positive cells in cerebrospinal fluid of patients with HTLV-I associated myelopathy. J Neuroimmunol 1993;42:127-130.
17. Nishimoto N, Yoshizaki K, Eiraku N et al. Elevated levels of interleukin-6 in serum and cerebrospinal fluid of HTLV-I associated myelopathy/ tropical spastic paraparesis. J Neurol Sci 1990;97:183-193.
18. Puccioni-Sohler. Immunologic parameters of cerebrospinal fluid in HTLV-I associated myelopathy (Abstract). Thesis. Gõttingen, Alemanha, 1994. Arq Neuropsiquiatr 1995;53:348-349.
19. Puccioni-Sohler M, Kitze B, Felgenhauer K. HTLV-I associated myelopathy in patients from Brazil and Iran. Arq Neuropsiquiatr 1995;53:213-217.
20. Puccioni-Sohler M, Kitze B, Felgenhauer K et al. The value of CSF analysis for the differential diagnosis of HTLV-I associated myelopathy and multiple sclerosis. Arq Neuropsiquiatr 1995,53:760-765.
21. Puccioni-Sohler M, Rieckmann P, Kitze B, Lange P, Albrecht M, Felgenhauer K. A soluble form of tumor necrosis factor receptor in cerebrospinal fluid and serum of HTLV-I-associated myelopathy and other neurological diseases. J Neurol 1995;242:239-242.
22. Robbins DS, Shirazi Y, Drysdale BE, Lieberman A, Shin ML. Production of cytotoxic factor for oligodendrocytes by stimulated astrocytes. J Immunol 1987;139:2593-2597.
23. Selmaj KW, Raine CS. Tumor necrosis factor mediates myelin and oligodendrocyte damage in vitro. Ann Neurol 1988;23:339-346.
24. Spina-França A, Livramento JA, Machado LR, Gomes HR, Vianna LS. HTLV-I antibodies in serum and cerebrospinal fluid in tropical spastic paraparesis in Brazil. Arq Neuropsiquiatr 1990;48:441 -447.
25. Tendler CL, Greenberg SJ, Burton JD et al. Cytokine induction in HTLV-I. J Cell Biochem 1991 ;46:302-311.
26. Tsukada N, Miyaghi K, Matsuda M, Yanagisawa N. Increased levels of circulating intercellular adhesion molecule-1 in multiple sclerosis and human T-lymphotropic virus type I-associated myelopathy. Ann Neurol 1993,33:646-649.
27. Vries HE, Moor ACE, Bloom-Roosemalen MCM et al. Lymphocyte adhesion to brain capillary endothelial cells in vitro. J Neuroimmunol 1994;52:1-8.

Análise do líquido cefalorraqueano e neuropatogênese da infecção pelo HTLV-I

Cerebrospinal fluid analysis and the pathogenesis of central nervous system infection by HTLV-I

Datas de Publicação

Publicação nesta coleção
10 Nov 2010
Data do Fascículo
1997

This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

[1] 1. Aderka D, Engelmann H, Shemer-Avni Y et al. Variation in serum levels of the soluble TNF receptors among healthy individuals. Lymphokine Cytokine Res1992; II: 157-159.

[2] 2. Aderka D, Wysenbeek A, Engelmann H et al. Correlation between serum levels of soluble tumor necrosis factor receptor and disease activity in systemic lupus erythematosus. Arth Rheumat 1993;36:1111-1120.

[3] 3. Cavalcanti M, Ferreira O, Puccioni M, No vis S, Schechter M. HTLV-I associated neurologic manifestations in four generations of a Brazilian family. J AIDS 1993;6:213-217.

[4] 4. Ceroni M, Picardo P, Rodgers- Johnson P et al. Intrathecal synthesis of IgG antibodies to HTLV-I supports an etiological role for HTLV-I in tropical spastic paraparesis. Ann Neurol 1988,23 (Suppl):S188-S191.

[5] 5. Chang Y, Allbright S, Lee F. Cytokines in the central nervous system: expression of macrophage colony stimulating factor and its receptor during development. J Neuroimmunol 1994;52:9-17.

[6] 6. Doukas J, Pober JS. IFN-gamma enhances endothelial activation induced by tumor necrosis factor but not IL-1. J Immunol 1990;145:1727-1733.

[7] 7. Gessain A, Caudie C, Gout O et al. Intrathecal synthesis of antibodies to human T lymphotropic virus type I and the presence of IgG oligogoclonal bands in the cerebrospinal fluid of patients with endemic tropical spastic paraparesis. J Infect Dis 1988;157:1226-1234.

[8] 8. Girardin E, Roux-Lombard P, Grau GE, Suter P, Gallati H. Imbalalance between rumour necrosis factor-alpha and soluble TNF receptor concentrations in severe meningococcaemia. Immunology 1992;76:20-23.

[9] 9. Godfried MH, van-der-Poll T, Jansen J et al. Soluble receptors for tumor necrosis factor: a putative marker of disease progression in HIV infection. AIDS 1993,7:33-36.

[10] 10. Grimaldi LM, Roos RP, Devare SG et al. HTLV-I associated myelopathy: oligoclonal immunoglobulin G bands contain anti-HTLV-I p24 antibody. Ann Neurol 1988,24:727-731.

[11] 11. Hõllsberg P, Hafler DA. Pathogenesis of diseases induced by human lymphotropic virus type I infection. N Engl J Med 1993;328:1173-1182.

[12] 12. Hughes CCW, Male DK, Lantos PL. Adhesion of lymphocytes to cerebral microvascular cells: effects of interferon-gamma, tumor necrosis factor and interleukin-1. Immunology 1988;64:677-681.

[13] 13. Kira J -I, Itoyama Y, Koyanagi Y et al. Presence of HTLV-I proviral DNA in central nervous system of patients with HTLV-I associated myelopathy. Ann Neurol 1992,31:39-45.

[14] 14. Mohler KM, Torrance DS, Smith Ca et al. Soluble tumor necrosis factor receptors are effective therapeutic agents in lethal endothoxemia and function simultaneously as both TNF carriers and TNF antagonists. J Immunol 1993; 151:1548-1561.

[15] 15. Nagasato K, NakamuraT, Ohishi K et al. Active production of anti-human T-lymphotropic virus type I (HTLV-I) IgM antibody in HTLV-I associated myelopathy. J Neuroimmunol 1991 ;32:105-109.

[16] 16. Nakamura S, Nagano I, Yoshioka M, Shimazaki S, Onodera J, Kogure K. Detection of tumor necrosis factor-a-positive cells in cerebrospinal fluid of patients with HTLV-I associated myelopathy. J Neuroimmunol 1993;42:127-130.

[17] 17. Nishimoto N, Yoshizaki K, Eiraku N et al. Elevated levels of interleukin-6 in serum and cerebrospinal fluid of HTLV-I associated myelopathy/ tropical spastic paraparesis. J Neurol Sci 1990;97:183-193.

[18] 18. Puccioni-Sohler. Immunologic parameters of cerebrospinal fluid in HTLV-I associated myelopathy (Abstract). Thesis. Gõttingen, Alemanha, 1994. Arq Neuropsiquiatr 1995;53:348-349.

[19] 19. Puccioni-Sohler M, Kitze B, Felgenhauer K. HTLV-I associated myelopathy in patients from Brazil and Iran. Arq Neuropsiquiatr 1995;53:213-217.

[20] 20. Puccioni-Sohler M, Kitze B, Felgenhauer K et al. The value of CSF analysis for the differential diagnosis of HTLV-I associated myelopathy and multiple sclerosis. Arq Neuropsiquiatr 1995,53:760-765.

[21] 21. Puccioni-Sohler M, Rieckmann P, Kitze B, Lange P, Albrecht M, Felgenhauer K. A soluble form of tumor necrosis factor receptor in cerebrospinal fluid and serum of HTLV-I-associated myelopathy and other neurological diseases. J Neurol 1995;242:239-242.

[22] 22. Robbins DS, Shirazi Y, Drysdale BE, Lieberman A, Shin ML. Production of cytotoxic factor for oligodendrocytes by stimulated astrocytes. J Immunol 1987;139:2593-2597.

[23] 23. Selmaj KW, Raine CS. Tumor necrosis factor mediates myelin and oligodendrocyte damage in vitro. Ann Neurol 1988;23:339-346.

[24] 24. Spina-França A, Livramento JA, Machado LR, Gomes HR, Vianna LS. HTLV-I antibodies in serum and cerebrospinal fluid in tropical spastic paraparesis in Brazil. Arq Neuropsiquiatr 1990;48:441 -447.

[25] 25. Tendler CL, Greenberg SJ, Burton JD et al. Cytokine induction in HTLV-I. J Cell Biochem 1991 ;46:302-311.

[26] 26. Tsukada N, Miyaghi K, Matsuda M, Yanagisawa N. Increased levels of circulating intercellular adhesion molecule-1 in multiple sclerosis and human T-lymphotropic virus type I-associated myelopathy. Ann Neurol 1993,33:646-649.

[27] 27. Vries HE, Moor ACE, Bloom-Roosemalen MCM et al. Lymphocyte adhesion to brain capillary endothelial cells in vitro. J Neuroimmunol 1994;52:1-8.