Reduction in glial immunity and neuropathology by a PAF antagonist and an MMP and TNFalpha inhibitor in SCID mice with HIV-1 encephalitis.
The effects of anti-inflammatory drugs on glial immunity and neuropathology were determined in a severe combined immune deficiency (SCID) mouse model of HIV-1 encephalitis. HIV-1-infected human monocyte-derived macrophages (MDM) are stereotactically inoculated into basal ganglia resulting in a multinucleated giant cell encephalitis. A platelet activating factor antagonist and a matrix metalloproteinase inhibitor, which also inhibits tumor necrosis factor alpha release, were administered to animals at the time of the MDM inoculation. The drugs administered in combination markedly reduced brain inflammation, astrogliosis and microglia activation. These findings demonstrate that reduction of brain inflammatory responses, independent of viral replication, can affect HIVE pathology in an animal model system of disease.
The Center for Neurovirology and Neurodegenerative Disorders, University of Nebraska Medical Center, 985215 Nebraska Medical Center, Omaha, NE 68198-5215, USA. ypersids@unmc.edu
Y
Y
Persidsky
J
J
Limoges
J
J
Rasmussen
J
J
Zheng
A
A
Gearing
H E
HE
Gendelman
D015526:AIDS Dementia Complex / Q000188:drug therapy / Q000276:immunology*; D000818:Animals; D001593:Benzyl Compounds; D002470:Cell Survival / Q000276:immunology; D003907:Dexamethasone / Q000494:pharmacology; D004195:Disease Models, Animal; D004338:Drug Combinations; D005911:Gliosis / Q000276:immunology; D015497:HIV-1; D006801:Humans; D066298:In Vitro Techniques; D007375:Interleukin-1 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D007930:Leucine / Q000031:analogs & derivatives / Q000494:pharmacology; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D061965:Matrix Metalloproteinase Inhibitors; D051379:Mice; D016513:Mice, SCID; D017628:Microglia / Q000276:immunology* / Q000473:pathology / Q000821:virology; D009474:Neurons / Q000276:immunology / Q000473:pathology; D010431:Pentoxifylline / Q000494:pharmacology; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D011480:Protease Inhibitors / Q000494:pharmacology; D013386:Succinates; D016212:Transforming Growth Factor beta / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000096:biosynthesis
C101468:BB 1101; C094498:BB 882; D001593:Benzyl Compounds; D004338:Drug Combinations; D007375:Interleukin-1; D016209:Interleukin-8; D061965:Matrix Metalloproteinase Inhibitors; D010972:Platelet Activating Factor; D011480:Protease Inhibitors; D013386:Succinates; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D003907:Dexamethasone; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D007930:Leucine; D010431:Pentoxifylline