Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P05231 (interleukin-6)
 23,907 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The clinical features, the underlying CIAS1 mutation, and the results of cytokine analyses are described for a 10-year-old German boy with neonatal-onset multisystem inflammatory disease, whose condition improved with age. Disease onset occurred at 26 months of age with predominantly cutaneous (urticarial rash) and neurologic (headache, chronic meningitis) symptoms including early bilateral optic nerve atrophy, whereas articular manifestations were mild. Sequence analysis of exon 3 of the CIAS1 gene revealed heterozygosity for a novel missense mutation. A T515C transition led to the replacement of isoleucine by threonine at amino acid position 172 (I172T) in a region of cryopyrin flanking the PYRIN and NACHT domains. This mutation was not present in the parents or in 11 controls and therefore was considered to be a de novo mutation. Enzyme-linked immunosorbent assays were performed to determine interleukin-6 and soluble tumor necrosis factor receptor superfamily 1B levels in the patient's serum and cerebrospinal fluid (CSF). Concentrations were highly elevated in the CSF, whereas corresponding serum levels remained low. The strong cytokine activation in the CSF corresponded with the neurologic symptoms. Local activation of intrathecal macrophages may therefore be an important pathogenetic mechanism. CSF cytokine levels decreased to normal under corticosteroid and intrathecal methotrexate therapy. When the boy reached the age of 5.5 years, treatment was stopped, and he has remained relapse-free.
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PMID:A novel CIAS1 mutation and plasma/cerebrospinal fluid cytokine profile in a German patient with neonatal-onset multisystem inflammatory disease responsive to methotrexate therapy. 1523 84

Autoinflammatory diseases are rare illnesses characterized by apparently unprovoked inflammation without high-titer auto-antibodies or antigen-specific T cells. They may cause neurological manifestations, such as meningitis and hearing loss, but they are also characterized by non-neurological manifestations. In this work we studied a 30-year-old man who had a chronic disease characterized by meningitis, progressive hearing loss, persistently raised inflammatory markers and diffuse leukoencephalopathy on brain MRI. He also suffered from chronic recurrent osteomyelitis of the mandible. The hypothesis of an autoinflammatory disease prompted us to test for the presence of mutations in interleukin-1-pathway genes and to investigate the function of this pathway in the mononuclear cells obtained from the patient. Search for mutations in genes associated with interleukin-1-pathway demonstrated a novel NLRP3 (CIAS1) mutation (p.I288M) and a previously described MEFV mutation (p.R761H), but their combination was found to be non-pathogenic. On the other hand, we uncovered a selective interleukin-6 hypersecretion within the central nervous system as the likely pathogenic mechanism. This is also supported by the response to the anti-interleukin-6-receptor monoclonal antibody tocilizumab, but not to the recombinant interleukin-1-receptor antagonist anakinra. Exome sequencing failed to identify mutations in other genes known to be involved in autoinflammatory diseases. We propose that the disease described in this patient might be a prototype of a novel category of autoinflammatory diseases characterized by prominent neurological involvement.
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PMID:An autoinflammatory neurological disease due to interleukin 6 hypersecretion. 2343 7