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

Ibudilast (3-isobutyryl-2-isopropylpyrazolo[1,5-a]pyridine) is a nonselective inhibitor of cyclic nucleotide phosphodiesterase (PDE). It is widely used in Japan for improving prognosis and relieving symptoms in patients suffering from ischemic stroke or bronchial asthma. These clinical applications are based on the properties of ibudilast that inhibit platelet aggregation, improve cerebral blood flow and attenuate allergic reactions. The inhibition of platelet aggregation and vasodilatation by ibudilast may be due to synergistic elevation of intracellular cyclic nucleotides and release of nitric oxide (NO) or prostacyclin from endothelium, rather than direct inhibition of PDE5 or PDE3. Another important property of ibudilast is its antiinflammatory activity possibly associated with potent inhibition of PDE4. Combined with its relaxing effects on bronchial smooth muscle, antiinflammatory activity of ibudilast could favorably influence pathophysiology of asthma by antagonizing chemical mediators triggering asthmatic attacks. Ibudilast was also reported to significantly attenuate inflammatory cell infiltration in the lumbar spinal cord in an animal model of encephalomyelitis. Future investigations should include effects of ibudilast on inflammatory reactions between endothelium and blood cells, which may initiate the development of atherosclerosis.
Cardiovasc Drug Rev 2001
PMID:Ibudilast: a non-selective PDE inhibitor with multiple actions on blood cells and the vascular wall. 1160 39

Prostaglandin E2 constitutes a major cyclooxygenase-2-derived prostanoid produced at inflammatory sites. In vitro and in vivo data support its role as a modulator of inflammation. Prostaglandin E2 exerts anti-inflammatory effects by binding to one of its receptors, the prostaglandin E receptor 4 (EP4), thereby modulating macrophage and T lymphocyte functions that participate crucially in innate and adaptive immunity and tissue remodeling and repair. The activation of EP4 suppresses the release of cytokines and chemokines from macrophages and T cells, inhibits the proliferation and the activation of T cells, and induces T-cell apoptosis. Lack of EP4 in bone marrow-derived cells accelerates local inflammation in atherosclerotic and aneurysm lesions and increases the prevalence of aneurysm formation. An EP4 agonist promotes graft survival in allograft cardiac transplantation and dampens tissue damage after myocardial ischemia. Anti-inflammatory actions of EP4 agonism may benefit other inflammatory disorders, including colitis and gastric ulcers. By contrast, EP4 acts as a proinflammatory mediator in encephalomyelitis, skin inflammation, and arthritis by promoting T helper (Th) 1 differentiation and Th17 expansion. Overall, EP4 activation produces powerful anti-inflammatory responses in many experimental diseases, rendering EP4 agonists attractive agents to attenuate syndromes associated with inflammation.
J Cardiovasc Pharmacol 2012 Feb
PMID:Anti-inflammation therapy by activation of prostaglandin EP4 receptor in cardiovascular and other inflammatory diseases. 2169 32