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)

Over the last few years, a series of molecules known to play a function in metabolism has also been shown to play an important role in the regulation of the immune response. In this context, the adipocyte-derived hormone leptin has been shown to regulate the immune response in normal as well as in pathological conditions. More specifically, it has been shown that conditions of reduced leptin production (i.e., genetic leptin deficiency, anorexia nervosa, malnutrition) are associated with increased susceptibility to infections. Conversely, immune-mediated disorders such as autoimmune disorders are associated with increased secretion of leptin and production of proinflammatory, pathogenic cytokines. Leptin could represent the "missing link" among immune response, metabolic function, and nutritional status. Indeed, more recently, leptin-deficient mice have been shown to be resistant to a series of experimentally induced autoimmune disorders including experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis. Normal wild-type mice show increased secretion of leptin in serum upon EAE induction, and brain inflammatory infiltrates stain positive for leptin. Finally, leptin neutralization with leptin antagonists improves the EAE course by profoundly altering intracellular signaling of myelin-reactive T cells and increasing the number of regulatory forkhead/winged helix transcription factor 3(+)CD4(+) T cells. These data suggest that leptin can be considered as a link among immune tolerance, metabolic state, and autoimmunity and that strategies aimed at interfering with the leptin axis could represent innovative, therapeutic tools for autoimmune disorders.
 ...
PMID:The intricate interface between immune and metabolic regulation: a role for leptin in the pathogenesis of multiple sclerosis? 1855 6

The objective of this study was to detect interleukin-17 (IL-17), interferon-gamma (IFN-gamma), interleukin-4 (IL-4) and forkhead/winged helix transcription factor p3 (Foxp3) protein and gene expression of the optic nerve and to further explore the role of T helper cell subsets such as Th1, Th2, Th17 and Treg in the pathogenesis of optic neuritis in experimental autoimmune encephalomyelitis (EAE). Mice in C57BL/6 background were randomly divided into control and EAE groups. At days 11, 15 and 19 post-immunization, optic nerves were dissected for morphological study to detect IL-17, IFN-gamma and IL-4. Protein analysis was done by enzyme-linked immunosorbent assay, quantitative real-time polymerase chain reaction for measuring the gene expression of IL-17, IFN-gamma, IL-4 and Foxp3. Concentrations of IL-17 protein in the optic nerve were significantly up-regulated at 11 days post-immunization, and IFN-gamma protein concentrations at 19 days. Concentrations of IL-4 protein in the optic nerve declined slightly in 19 days. mRNA expression of IL-17, IFN-gamma and IL-4 was consistent with their protein expression. Foxp3 mRNA transcription was down-regulated at 11-19 days post-immunization. Decreased expression of Foxp3 mRNA and Treg in the optic nerve may play a key role in the development of optic neuritis. IL-17 may mediate inflammatory pathogenicity at the early stage of optic neuritis, and IFN-gamma may aggravate inflammatory injury during the peak stage of optic neuritis.
 ...
PMID:Alteration of T helper cell subsets in the optic nerve of experimental autoimmune encephalomyelitis. 2042 90