Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0014070 (encephalomyelitis)
 13,017 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Insulin-like growth factor (IGF)-1 is a cytokine that promotes oligodendrocyte development and myelin production. This study investigated whether treatment of chronic, relapsing murine experimental autoimmune encephalomyelitis (EAE) with IGF-1 or IGF-1 associated with its binding protein, IGFBP3, altered the course of disease. Administration of IGF-1/IGFBP3 (1-100 mg/kg per day) delayed the onset of disease in a dose-dependent manner and histologic examination showed a delay in inflammatory cells entering the central nervous system. However, once signs of EAE developed, disease was enhanced in the mice that had been given the highest dose of IGF-1/IGFBP3. Treatment with IGF-1/IGFBP3 after the onset of signs resulted in a severe relapse. Administration of free IGF-1 (10 mg/kg per day) provided mild protection when given before disease onset, but did not significantly alter the course of disease if given after disease onset. Possible mechanisms that could explain the altered disease in IGF-1/IGFBP3-treated mice included (a) IGF-1/IGFBP3 administration delayed the onset of EAE by downregulating ICAM-1 gene expression in the central nervous system, and (b) IGF-1/IGFBP3 treatment of EAE resulted in more severe disease due to enhanced expansion of encephalitogenic T cells. Although IGF-1 may enhance remyelination, these results indicate that administration of IGF-1 associated with IGFBP3 may also accentuate autoimmune demyelinating disease.
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PMID:Regulation of experimental autoimmune encephalomyelitis with insulin-like growth factor (IGF-1) and IGF-1/IGF-binding protein-3 complex (IGF-1/IGFBP3). 954 12

Insulin-like growth factor 1 increases both the number of oligodendrocytes and the amount of axonal myelin produced. The aim of this study was to see whether insulin-like growth factor 1 played a role in white-matter diseases of children. We studied insulin-like growth factor 1 in the cerebrospinal fluid of children with various white-matter diseases: (1) children with acute demyelinating events: acute disseminated encephalomyelitis (n = 5), acute transverse myelitis in multiple sclerosis (n = 1), and infarct of the medial cerebral artery causing secondary white-matter changes (n = 1), and (2) children with chronic diseases: delayed myelination (n = 3) and progressive leukodystrophies (n = 4). Insulin-like growth factor 1 was determined by radioimmunoassay with commercially available kits (Mediagnost, Tubingen, Germany). We found markedly lower concentrations of cerebrospinal fluid insulin-like growth factor 1 in the patients than in the 28 age-matched control children (P < .0005). Low cerebrospinal fluid insulin-like growth factor 1 can play a role in the pathology of both acute and chronic white-matter diseases of children.
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PMID:Cerebrospinal fluid insulin-like growth factor 1 is low in acute and chronic white-matter diseases of children. 1583 5

Insulin-like growth factor 1 (IGF-1) has been identified as a critical molecule in the induction of myelination in the central nervous system (CNS). Systemic injection of IGF-1 has been shown to have a varied and transiently protective effect on the clinical course of experimental autoimmune encephalomyelitis (EAE). Since systemic IGF-1 can also modulate peripheral immune lymphocytes, we examined whether a sustained and local delivery of IGF-1 into the spinal cord would have any influence on the chronic course of EAE in C57/BL6 mice. The capability of adeno-associated virus (AAV) to be retrogradely transported efficiently from muscle to motor neurons of the spinal cord was used to overcome the difficulty routinely encountered when attempting chronic delivery of molecules into the CNS. We demonstrate that AAV-mediated delivery of IGF-1 in CNS did not have any beneficial effect on the clinical course of EAE. Injection of AAV-IGF1 after induction of the disease worsened the clinical symptoms. Furthermore, CNS expression of IGF-1 did not affect the pathogenic anti-MOG T cell response, as examined by proliferation and cytokine secretion. Thus, enhanced expression of IGF-1 in the CNS during inflammation does not have a significant effect on myelination. These data have important implications for the potential use of IGF-1 in the treatment of multiple sclerosis.
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PMID:Targeted expression of IGF-1 in the central nervous system fails to protect mice from experimental autoimmune encephalomyelitis. 1612 Apr 66

The mechanism by which tolerance is broken in the induction of autoimmunity is unknown. Simple, well-characterized antigens suggest that molecular complementarity may play a key role in breaking tolerance. Experimental allergic encephalomyelitis can be induced using myelin basic protein combined with muramyl dipeptide. These molecules bind specifically to each other. Insulin antibodies can be induced when insulin is combined with glucagon, to which it binds. These cases suggest that molecular complementarity may alter the processing of "self" proteins. Antigenic complementary yields molecularly complementary immune responses (i.e., idiotypic-anti-idiotypic), undermining immune system regulation. In addition, complementarity insures that the antibodies (or T cells) directed against one antigen will molecularly mimic the other antigen, and vice versa, so that "self" and "nonself" will be confused. If at least one complementary antigen mimics a "self" protein, then an unregulated, self-sustaining immune response against tissue results. This testable theory of antigenic complementarity in autoimmunity is reviewed.
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PMID:Antigenic complementarity in the induction of autoimmunity: a general theory and review. 1741 97