ABSTRACT
Intracellular production of TNFalpha and IL-2 after stimulation with phorbol myristate/ionomycin was flowcytometrically measured in CD4(+) T cells from peripheral blood (PB) and cerebrospinal fluid (CSF) of 29 patients with multiple sclerosis (MS), and 16 with other inflammatory and 41 with other non-inflammatory neurological diseases. In CSF, the percentages of CD4(+)TNFalpha(+)IL-2(-)T cells were significantly higher in patients with MS than either of the controls, whereas no difference was found in CD4(+)TNFalpha(+)IL-2(+)T or CD4(+)TNFalpha(-)IL-2(+)T cells. The increase was more pronounced at relapse than in remission. No significant change was detected in PB. These findings suggested that CD4(+)TNFalpha(+)IL-2(-)T cells are intrathecally upregulated in MS.
Subject(s)
CD4-Positive T-Lymphocytes/metabolism , Interleukin-2/metabolism , Multiple Sclerosis, Relapsing-Remitting/immunology , Tumor Necrosis Factor-alpha/metabolism , Adult , Aged , CD4-Positive T-Lymphocytes/pathology , Cerebrospinal Fluid/cytology , Cerebrospinal Fluid/immunology , Female , Flow Cytometry , Humans , Male , Middle Aged , Multiple Sclerosis, Relapsing-Remitting/cerebrospinal fluid , Multiple Sclerosis, Relapsing-Remitting/pathologyABSTRACT
BACKGROUND: We reported the emergence of a distinct myelitis in patients with atopic diathesis (atopic myelitis [AM]) by a nationwide survey throughout Japan. Similar cases have recently been reported in Caucasians. Pathologic studies of biopsied spinal cord specimens revealed chronic active inflammation with eosinophilic infiltration. OBJECTIVE: To clarify the cytokine/chemokine alterations in CSF from patients with AM in comparison to other causes of myelitis. METHODS: We measured 27 cytokines, chemokines, and growth factors simultaneously in CSF from 22 patients with AM, 20 with opticospinal multiple sclerosis (OSMS), 11 with HTLV-1-associated myelopathy (HAM), 9 with Sjögren syndrome-related myelitis (SM), and 20 with other noninflammatory neurologic diseases (OND), using a fluorescent bead-based immunoassay. RESULTS: In patients with AM, CCL11 and interleukin (IL)-9 were significantly increased as compared with patients with OND and other myelitis while in patients with OSMS interferon-gamma and granulocyte-colony stimulating factor levels were significantly higher than in patients with OND and other causes of myelitis. Significant increase of IL-17 in comparison to patients with OND was found only in patients with OSMS, irrespective of presence or absence of anti-aquaporin-4 (AQP4) antibody. In patients with HAM, CXCL10 and CCL5 were higher than in patients with OND and other myelitis. In patients with SM, CCL3 and CCL4 were higher than in patients with OND. In patients with AM, CCL11, IL-9, and IL-1 receptor antagonist (IL-1ra) showed positive correlations with the final Kurtzke Expanded Disability Status Scale scores while IL-1ra and IL-12(p70) had positive correlations with disease duration. CONCLUSION: Intrathecal upregulation of CCL11 and Th2 cytokines is characteristic of atopic myelitis, which is distinct from interleukin-17/interferon-gamma-related autoimmune condition of opticospinal multiple sclerosis.
