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

Cytokines are powerful mediators of biologic responses in the CNS and may contribute to cellular injury in pathophysiologic states. In order to better understand the actions of cytokines in the intact mammalian CNS, a transgenic approach was employed that targeted the expression of different cytokines to astrocytes in mice. Fusion gene constructs consisting of a GFAP expression vector into which was inserted the DNA encoding the cytokines interleukin-6 (IL-6), IL-3, or TNF-alpha were used to generate transgenic mice. Expression of the transgene-encoded cytokines in astrocytes was confirmed at both the RNA and protein levels. Transgenic mice were subject to multilevel analysis to determine the extent of structural and functional CNS alterations. Transgenic mice exhibited distinct adult-onset, chronic-progressive neurological disorders that correlated with the level and anatomic distribution of transgene-encoded cytokine expression. The principal findings were neurodegeneration and cognitive decline due to IL-6 expression, macrophage/microglial-mediated primary demyelination with motor disease resulting from IL-3 expression, and lymphocytic meningoencephalomyelitis with paralysis induced by TNF-alpha expression. These transgenic models (1) indicate that expression of cytokines per se in the intact CNS is pathogenic, with cytokine-specific neural cell injury leading to unique functional deficits; (2) recapitulate many of the structural and functional changes seen in human inflammatory neurological disorders; (3) provide a valuable tool for advancing our understanding of the CNS pathobiology of cytokines; and (4) offer a unique resource for the development and testing of therapies aimed at abrogating the harmful actions of these important mediators.
 ...
PMID:Structural and functional impact of the transgenic expression of cytokines in the CNS. 962 40

Serial changes in the circulating and cerebrospinal fluid (CSF) cytokine levels were assessed in a patient with Sjogren's syndrome (SS)-associated meningoencephalomyelitis. A 16-yr-old girl diagnosed as having primary SS at 8 yr of age presented headache and vomiting. CSF studies revealed lymphocyte-dominant pleocytosis and high IgM index, but no evidence of infection. Disturbed consciousness and diffuse slow waves on electroencephalogram led to the diagnosis of SS-meningoencephalitis. The clinical condition subsided after a cycle of dexamethasone therapy, however, 2 months later urinary retention and paresthesia of the lower body developed. Craniospinal magnetic resonance imaging (MRI) showed extensive intraparenchymal lesions with high T2-weighted signal intensity adjacent to the posterior left horn of lateral ventricle of the brain and the longitudinal lesion from C5 to T10 of the spinal cord. High-dose methyl-prednisolone and subsequent tacrolimus therapy has effectively controlled the activity of SS-meningoencephalomyelitis. Monitoring of systemic and CSF cytokine levels during the course of illness revealed that CSF interleukin-6, but not interferon-gamma or tumor necrosis factor-alpha levels were the sensitive indicator of disease activity. The unique cytokine profile, differing from those of infectious meningitis may be useful for predicting the central nervous system involvement in autoimmune disease.
 ...
PMID:Sjogren's syndrome-associated meningoencephalomyelitis: cerebrospinal fluid cytokine levels and therapeutic utility of tacrolimus. 1799 6