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)

Increasing evidence shows that oxidative stress plays an important role in the pathogenesis of multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE). In recent years, bilirubin has been demonstrated to be a potent antioxidant in vitro. In this study, we administered bilirubin to rats with acute and chronic EAE. Bilirubin prevented both acute and chronic EAE effectively. More significantly, bilirubin suppressed ongoing clinical EAE and halted EAE progression when given after disease onset. Subsequent histological examination showed that if administered to rats before the onset of EAE, bilirubin interfered with the invasion of inflammatory cells into the central nervous system (CNS) because it protected the blood-brain barrier (BBB) from free radical-induced permeability changes. However, in some cases, inflammation still occurred even when no clinical illness was observed. In rats with treatment initiated after the onset of EAE, despite the clinical improvements, treatment with bilirubin did not reduce the degree of CNS inflammation, or change cytokine expression in CNS lesions, indicating a lack of immunosuppressive effect of this treatment. By contrast, bilirubin treatment significantly alleviated oxidative damage in the spinal cord, and the clinical signs of EAE correlated well with the degree of oxidative injury in the lesions. Our results suggest that free radicals play an important role in the final effector stages of EAE, and that antioxidant therapies may have potential for the treatment of MS.
 ...
PMID:Bilirubin as a potent antioxidant suppresses experimental autoimmune encephalomyelitis: implications for the role of oxidative stress in the development of multiple sclerosis. 1279 17

Oxidative stress plays an important role in the pathogenesis of multiple sclerosis and its animal model, experimental autoimmune encephalomyelitis (EAE). Bilirubin is regarded today as a potent antioxidant. Recent studies show that the potent antioxidant actions of bilirubin reflect an amplification mechanism whereby biliverdin reductase (BVR) physiologically regenerates bilirubin in a catalytic cycle. We hypothesized that BVR might prove to be a new effective target for the treatment of free radical-mediated diseases. In this study, we demonstrated that treatment with BVR ameliorated both clinical and pathological signs of EAE more efficiently than treatments with traditional antioxidant enzymes. In vitro, interference with cellular BVR activity by siRNA elicited greater increases in reactive oxygen species and cell death than interference with the activities of other antioxidant enzymes. Further studies showed that BVR surpasses other enzymes by the multifactorial functions of its only end product, bilirubin, including anti-complement activity, and an activity that inhibits antibody-dependent cell-mediated cytotoxicity of lymphocytes. Since BVR regenerates bilirubin in a redox cycle without significantly increasing the concentration of bilirubin, our results suggest that BVR may represent a novel strategy for the treatment of multiple sclerosis and other oxidative stress-mediated diseases.
 ...
PMID:Biliverdin reductase, a major physiologic cytoprotectant, suppresses experimental autoimmune encephalomyelitis. 1654 Mar 91

Bilirubin, an abundant bile pigment in mammalian serum, was once considered a toxic waste product and has more recently been recognized as a potent antioxidant of physiological importance. However, its potential biological functions in other fields are not well understood. Herein we show that bilirubin is also a powerful immunomodulatory agent. Bilirubin significantly inhibited Ag-specific and polyclonal T cell responses, while other similar antioxidants completely lacked this effect. Bilirubin suppressed CD4(+) T cell responses at multiple steps. High levels of bilirubin could induce apoptosis in reactive CD4(+) T cells. Bilirubin at nonapoptotic concentrations suppressed CD4(+) T cell reactivity through a wide range of actions, including inhibition of costimulator activities, suppression of immune transcription factor activation, and down-regulation of inducible MHC class II expression. Further studies suggest that bilirubin actions were direct, rather than via induction of immune deviation or regulatory T cells. In vivo, treatment with bilirubin effectively suppressed experimental autoimmune encephalomyelitis in SJL/J mice. In contrast, depletion of endogenous bilirubin dramatically exacerbated this disease. In summary, our results identify bilirubin as an important immunomodulator that may protect mammals against autoimmune diseases, thereby indicating its potential in the treatment of multiple sclerosis and other immune disorders.
 ...
PMID:Bilirubin possesses powerful immunomodulatory activity and suppresses experimental autoimmune encephalomyelitis. 1864 26

Bilirubin is the end product of heme catabolism by heme oxygenases. Although bilirubin has long been considered as a toxic waste product, it is now recognized as an endogenous antioxidant. It has been reported that bilirubin is an effective treatment in both acute and chronic experimental autoimmune encephalomyelitis (EAE) disease models. However, the relationship between bilirubin and multiple sclerosis (MS) has not been fully explored. The serum bilirubin concentrations were measured in 340 individuals comprising 88 healthy subjects, 133 patients with MS and 119 patients with cerebral infarction. Serum total bilirubin (Tbil), direct bilirubin (Dbil) and indirect bilirubin (Ibil) concentrations were significantly lower in patients with MS than in either patients with cerebral infarction or healthy controls (p<0.001). The correlation identified between bilirubin and MS was still highly significant when the effect of gender was eliminated. Among patients with MS, Tbil, Dbil and Ibil concentrations were lower in patients with MS with longer duration (>2 years), less disabling disease (Expanded Disability Status Scale score<3), and inactive MRI appearance, although the differences did not reach statistical significance. Our results suggest that there are reduced serum bilirubin concentrations in patients with MS.
 ...
PMID:Serum bilirubin concentrations and multiple sclerosis. 2178 48