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)

Experimental allergic encephalomyelitis (EAE) is an autoimmune inflammatory disease of the central nervous system (CNS). It is an animal model of post-infectious encephalomyelitis and multiple sclerosis (MS). Acute EAE is mediated by macrophages and by T helper 1 (Th1) lymphocytes directed against brain antigens. Inflammation in EAE could potentially be modified by prostaglandins (PG) secreted by blood monocytes (Mo) and brain glial cells. PGE elevates cAMP, which inhibits Mo function and selectively blocks secretion of cytokines by Th1 cells. In the present study, we found that a long-acting PGE1 analogue (LAPGE) inhibited clinical and histological EAE. Indomethacin (INDO) also suppressed active EAE. The combination of INDO plus LAPGE inhibited disease further, possibly by allowing LAPGE to function unopposed by immunostimulatory PG. EAE was suppressed when these agents were administered from the time of immunization or from the onset of clinical disease. The combination of INDO plus LAPGE also inhibited delayed-type hypersensitivity (DTH) reactions to myelin basic protein (MBP), and diminished in vitro lymphocyte responses to mitogens and MBP. PGE analogues and modifiers of arachidonate metabolism block autoimmune responses to brain antigens in vitro and in vivo, and may ameliorate inflammatory and autoimmune diseases of the brain and other organs.
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PMID:Prostaglandins and inhibitors of arachidonate metabolism suppress experimental allergic encephalomyelitis. 752 42

Experimental allergic encephalomyelitis (EAE) is an autoimmune inflammatory disease of the brain and spinal cord. It is an animal model of postinfectious encephalomyelitis and multiple sclerosis (MS). In EAE and in MS, monocytes and Th1 lymphocytes penetrate the blood-brain barrier, and the ensuing inflammation causes demyelination and death of oligodendroglia. PGE is a product of blood Mo and of brain glial cells that affects immune regulation. PGE and other cAMP agonists inhibit monocyte function and secretion of cytokines by Th1 cells. However, they have minimal effects on some cytokines secreted by Th2 cells. We hypothesized that eicosenoids would inhibit central nervous system inflammation mediated by Th1 cells. We found that misoprostol, a long-acting PGE1 analog, inhibited clinical and histological signs of moderately severe EAE in Lewis rats. Indomethacin also suppressed EAE and enhanced the LAPGE effect. Both agents suppressed EAE when administered either from the time of immunization or from the onset of clinical disease. The combination of misoprostol and indomethacin inhibited delayed-type hypersensitivity reactions to MBP (a Th1 response). These agents also inhibited in vitro lymphocyte proliferation to mitogens and MBP. Leukotrienes (LKT) elevate intracellular cGMP and amplify immune responses, the opposite of cAMP agonists. We found that LKT synthesis inhibitors blocked EAE, presumably by lowering levels of cGMP in inflammatory cells. Reduction of LKT synthesis enhanced the effects of misoprostol plus indomethacin on EAE. PGE analogs, indomethacin, and inhibitors of LKT synthesis block autoimmune responses to brain antigens in vitro and in vivo. Modification of intracellular cAMP and cGMP levels with these agents may ameliorate inflammatory and autoimmune diseases.
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PMID:Eicosenoids Modify Experimental Allergic Encephalomyelitis. 1185 49