Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0030552 (paresis)
 5,831 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cytokine production by T cells in the cerebrospinal fluid (CSF) and central nervous system (CNS) of SJL/J mice during myelin basic protein (MBP)-induced experimental allergic encephalomyelitis (EAE) was examined. Reverse transcriptase/polymerase chain reaction (RT/PCR) was used to measure interleukin-2 (IL-2) and interferon-gamma (IFN-gamma) mRNA levels from perfused CNS tissue (brain and spinal cord) and from cells isolated from CSF. Animals were grouped according to EAE severity, ranging from asymptomatic (adjuvant only) to severe disease (paralysis or severe paresis). Cytokine signals, normalized to actin, were almost undetectable in control tissues, and only slightly elevated in whole CNS tissue from animals with mild EAE. Both cytokine messages were strongly upregulated in CNS tissues derived from severely affected animals, consistent with previous observations correlating disease progression with infiltration by memory/effector CD4+ T cells, the major source of these cytokines. This cytokine upregulation was specific to the CNS, since other organs from the same animals did not express significant levels of IL-2 and IFN-gamma. CSF was obtained from the cisterna magna of unperfused mice and verified as such by absence of red blood cells (RBCs) and by immunoglobulin concentration orders of magnitude lower than in serum. Cytokine message was measured in RNA isolated from cells in CSF. Levels of IL-2 and IFN-gamma mRNA in CSF cells were significantly elevated in mild EAE and strongly upregulated in severe disease, correlating with those in total CNS tissue. These results confirm the CSF as representative of the immune status of the CNS and indicate a role for IL-2 and IFN-gamma in inflammatory CNS disease.
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PMID:Cytokine production by cells in cerebrospinal fluid during experimental allergic encephalomyelitis in SJL/J mice. 829 48

Axonal damage is the major cause of irreversible neurologic disability in patients with multiple sclerosis. Although axonal damage correlates with antibodies against neurofilament light (NF-L) protein, a major component of the axonal cytoskeleton, the possible pathogenic role of autoimmunity to axonal antigens such as NF-L has so far been ignored. Here we show that Biozzi ABH mice immunized with NF-L protein develop neurologic disease characterized by spastic paresis and paralysis concomitant with axonal degeneration and inflammation primarily in the dorsal column of the spinal cord. The inflammatory central nervous system lesions were dominated by F4/80+ macrophages/microglia and relatively low numbers of CD4+ and CD8+ T-cells. In splenocyte cultures, proliferation to NF-L was observed in CD4+ T-cells accompanied by the production of the proinflammatory cytokine interferon-gamma. Elevated levels of circulating antibodies recognizing recombinant mouse NF-L were present in the serum, and immunoglobulin deposits were observed within axons in spinal cord lesions of mice exhibiting clinical disease. These data provide evidence that autoimmunity to NF-L protein induces axonal degeneration and clinical neurologic disease in mice, indicating that autoimmunity to axonal antigens, as described in multiple sclerosis, may be pathogenic rather than acting merely as a surrogate marker for axonal degeneration.
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PMID:Immunization with neurofilament light protein induces spastic paresis and axonal degeneration in Biozzi ABH mice. 1741 20