Cytokine dysregulation in HIV-associated neurological disease.
AIDS is associated with three major neurological syndromes: dementia (HIVD), vacuolar myelopathy (VM) and plainful sensory neuropathy (PSN). The pathogenesis of these conditions remains unclear although they all demonstrate a marked increase in macrophage number and activation despite systemic immunosuppression. It was therefore of interest to determine the profile of cytokine and HIV expression in brain, spinal cord and peripheral nerves of AIDS patients with AD, VM and PSN, as compared to AIDS patients without neurological disease and seronegative controls. RNA was extracted from brain, spinal cord and peripheral nerve and RT/PCR for cytokine and HIV mRNA was performed. In situ RT/PCR was performed to determine the number and type of cells expressing cytokine message and this was compared to the number of cells containing HIV DNA detected with in situ PCR. We found a consistent profile of increased TNF alpha and decreased IFN gamma and IL4 in all three syndromes compared to AIDS patients without neurological disease. IL1 did not increase in parallel with TNF alpha IL10 was decreased in the VM tissue. HIV transcripts were increased in the AD brains compared to non-demented controls but were detected only occasionally in spinal cord and not at all in peripheral nerve. Preliminary data from in situ RT/PCR suggests that a large number of cells are expressing. TNF alpha but only a small number are infected with HIV.(ABSTRACT TRUNCATED AT 250 WORDS)
Wesselingh
S L
SL
Department of Microbiology and Infectious Diseases, Flinders University of South Australia, Adelaide.
Glass
J
J
McArthur
J C
JC
Griffin
J W
JW
Griffin
D E
DE
D015526:AIDS Dementia Complex / Q000503:physiopathology*; D000163:Acquired Immunodeficiency Syndrome / Q000378:metabolism; D016207:Cytokines / Q000096:biosynthesis* / Q000235:genetics; D005786:Gene Expression Regulation; D015967:Gene Expression Regulation, Viral; D018023:HIV Seronegativity; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis / Q000235:genetics; D015847:Interleukin-4 / Q000172:deficiency; D007378:Interleukins / Q000096:biosynthesis / Q000235:genetics; D008262:Macrophage Activation; D008954:Models, Biological; D009420:Nervous System / Q000378:metabolism / Q000821:virology; D010523:Peripheral Nervous System Diseases / Q000378:metabolism; D016133:Polymerase Chain Reaction; D011453:Prostaglandins / Q000096:biosynthesis; D012333:RNA, Messenger / Q000032:analysis; D012367:RNA, Viral / Q000096:biosynthesis; D013118:Spinal Cord Diseases / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000235:genetics
D016207:Cytokines; D007378:Interleukins; D011453:Prostaglandins; D012333:RNA, Messenger; D012367:RNA, Viral; D014409:Tumor Necrosis Factor-alpha; D015847:Interleukin-4; D007371:Interferon-gamma