Tumor necrosis factor‐α messenger RNA expression in patients with relapsing‐remitting multiple sclerosis is associated with disease activity

We determined the cytokine messenger RNA (mRNA) expression pattern of blood mononuclear cells in 29 patients with relapsing‐remitting multiple sclerosis every 4 weeks over a period of 12 months. During this period 27 relapses occurred in 14 patients (48%). Progression of disease activity as assessed by the occurrence of new lesions on nonenhancing T2‐weighted magnetic resonance images of the head was detected in 12 (48%) of 25 patients. Using a semiquantitative polymerase chain reaction we demonstrated significant increases in tumor necrosis factor‐α mRNA expression in peripheral blood mononuclear cells prior to a relapse. In 24 (85%) of 27 relapses increased tumor necrosis factor‐α mRNA expression preceded clinical symptoms by 4 weeks. A similar pattern was observed for lymphotoxin mRNA expression. At the same time, transforming growth factor‐β and interleukin‐10 mRNA levels declined. Fluctuations in the mRNA expression of tumor necrosis factor‐αwere also observed in 6 patients with stable disease who had active magnetic resonance scans on follow‐up. No correlation of disease activity was observed with interleukin‐1β, ‐4, or ‐6, inferferon gamma or endothelin‐1 mRNA expression. From these data it can be concluded that variations in cytokine mRNA expression in blood mononuclear cells are correlated with disease activity in relapsing‐remitting multiple sclerosis. It may be a valuable parameter to monitor the immunological status of patients in future clinical trials.

[1]  A. Broocks,et al.  Cytokine mRNA levels in mononuclear blood cells from patients with multiple sclerosis , 1994, Neurology.

[2]  J. Taubenberger,et al.  Correlation between magnetic resonance imaging findings and lesion development in chronic, active multiple sclerosis , 1993, Annals of neurology.

[3]  A. Weinberg,et al.  Lymphokine mRNA expression in the spinal cords of Lewis rats with experimental autoimmune encephalomyelitis is associated with a host recruited CD45R hi/CD4+ population during recovery , 1993, Journal of Neuroimmunology.

[4]  C. Orosz,et al.  DETECTION OF CYTOKINE mRNA IN VIVO BY POLYMERASE CHAIN REACTION: PROBLEMS AND SOLUTIONS , 1993, Transplantation.

[5]  M. Huberman,et al.  Decreased IL-3 production by peripheral blood mononuclear cells in patients with multiple sclerosis , 1993, Journal of the Neurological Sciences.

[6]  H. Hartung Immune‐mediated demyelination , 1993, Annals of neurology.

[7]  G. Pizzolato,et al.  Immunopathological changes in human cerebral malaria. , 1993, Clinical neuropathology.

[8]  D. Paty,et al.  Interferon beta‐1b is effective in relapsing‐remitting multiple sclerosis , 1993, Neurology.

[9]  C. Poser The pathogenesis of multiple sclerosis , 1993, Journal of the Neurological Sciences.

[10]  R. McCarron,et al.  Cytokine-regulated adhesion between encephalitogenic T lymphocytes and cerebrovascular endothelial cells , 1993, Journal of Neuroimmunology.

[11]  G. Grau,et al.  Tumor necrosis factor alpha production as a possible predictor of relapse in patients with multiple sclerosis. , 1992, European cytokine network.

[12]  K. Mohler,et al.  Analysis of cytokine mRNA expression in the central nervous system of mice with experimental autoimmune encephalomyelitis reveals that IL-10 mRNA expression correlates with recovery. , 1992, Journal of immunology.

[13]  B. Bloom,et al.  Cytokine patterns of immunologically mediated tissue damage. , 1992, Journal of immunology.

[14]  E. Thompson,et al.  In vivo relationship of tumor necrosis factor-α to blood-brain barrier damage in patients with active multiple sclerosis , 1992, Journal of Neuroimmunology.

[15]  R. Rudick,et al.  Cytokine secretion by multiple sclerosis monocytes. Relationship to disease activity. , 1992, Archives of neurology.

[16]  V. Barnaba,et al.  Tumour necrosis factor‐alpha synthesis by cerebrospinal‐fluid‐derived T cell clones from patients with multiple sclerosis , 1991, Italian journal of neurological sciences.

[17]  Y. Shimamoto,et al.  Human tumor necrosis factor-α augments experimental allergic encephalomyelitis in rats , 1991, Journal of Neuroimmunology.

[18]  A. Cross,et al.  Anti—tumor necrosis factor therapy abrogates autoimmune demyelination , 1991, Annals of neurology.

[19]  K. Flanders,et al.  Successful treatment of experimental allergic encephalomyelitis with transforming growth factor-beta 1. , 1991, Journal of immunology.

[20]  M. Sharief,et al.  Association between Tumor Necrosis Factor-α and Disease Progression in Patients with Multiple Sclerosis , 1991 .

[21]  C. Raine Multiple sclerosis: a pivotal role for the T cell in lesion development , 1991, Neuropathology and applied neurobiology.

[22]  J. Trotter,et al.  Serum cytokine levels in chronic progressive multiple sclerosis: interleukin-2 levels parallel tumor necrosis factor-α levels , 1991, Journal of Neuroimmunology.

[23]  A. Reder,et al.  Cytokine levels in the cerebrospinal fluid and serum of patients with multiple sclerosis , 1991, Journal of Neuroimmunology.

[24]  C. Brosnan,et al.  Identification of lymphotoxin and tumor necrosis factor in multiple sclerosis lesions. , 1991, The Journal of clinical investigation.

[25]  W. Tourtellotte,et al.  Serum and CSF levels of IL‐2, sIL‐2R, TNF‐α, and IL‐1β in chronic progressive multiple sclerosis , 1991, Neurology.

[26]  R. Clark,et al.  An antibody to lymphotoxin and tumor necrosis factor prevents transfer of experimental allergic encephalomyelitis , 1990, The Journal of experimental medicine.

[27]  R J Albertini,et al.  T cells responsive to myelin basic protein in patients with multiple sclerosis. , 1990, Science.

[28]  J. Merrill,et al.  Tumor necrosis factor identified in multiple sclerosis brain , 1989, The Journal of experimental medicine.

[29]  B. Tavolato,et al.  Tumor necrosis factor alpha (TNFα) and neurological diseases Failure in detecting TNFα in the cerebrospinal fluid from patients with multiple sclerosis, AIDS dementia complex, and brain tumours , 1989, Journal of Neuroimmunology.

[30]  H. Weiner,et al.  MS: a CNS and systemic autoimmune disease. , 1989, Immunology today.

[31]  H. Kirchner,et al.  Increased production of interferon gamma and tumor necrosis factor precedes clinical manifestation in multiple sclerosis: Do cytokines trigger off exacerbations? , 1988, Acta neurologica Scandinavica.

[32]  W. Mcdonald The mystery of the origin of multiple sclerosis. , 1986, Journal of neurology, neurosurgery, and psychiatry.

[33]  B. Waksman Human disease: Mechanisms in multiple sclerosis , 1985, Nature.

[34]  J. Kurtzke Rating neurologic impairment in multiple sclerosis , 1983, Neurology.

[35]  E. Reinherz,et al.  Multiple sclerosis Distribution of T cells, T cell subsets and Ia-positive macrophages in lesions of different ages , 1983, Journal of Neuroimmunology.

[36]  D. Silberberg,et al.  New diagnostic criteria for multiple sclerosis: Guidelines for research protocols , 1983, Annals of neurology.