title: Murine immunodeficiency virus-induced peripheral neuropathy and the associated cytokine responses.
abstract: Distal symmetrical polyneuropathy is the most common form of HIV infection-associated peripheral neuropathy and is often associated with pain. C57BL/6 (B6) mice infected with LP-BM5, a murine retroviral isolate, develop a severe immunodeficiency syndrome similar to that in humans infected with HIV-1, hence the term murine AIDS. We investigated the induction of peripheral neuropathy after LP-BM5 infection in B6 mice. Infected B6 mice, like HIV-infected humans, exhibited behavioral (increased sensitivity to mechanical and heat stimuli) and pathological (transient loss of intraepidermal nerve fibers) signs of peripheral neuropathy. The levels of viral gag RNA were significantly increased in all tissues tested, including spleen, paw skin, lumbar dorsal root ganglia, and lumbar spinal cord, postinfection (p.i.). Correlated with the development of peripheral neuropathy, the tissue levels of several cytokines, including IFN-γ, IL-1β, IL-6, and IL-12, were significantly elevated p.i. These increases had cytokine-specific and tissue-specific profiles and kinetics. Further, treatment with the antiretroviral agent zidovudine either significantly reduced or completely reversed the aforementioned behavioral, pathologic, and cytokine changes p.i. These data suggest that LP-BM5 infection is a potential mouse model of HIV-associated distal symmetrical polyneuropathy that can be used for investigating the roles of various cytokines in infection-induced neuropathic pain. Further investigation of this model could give a better understanding of, and lead to more effective treatments for, HIV infection-associated painful peripheral neuropathy.
authors.affiliation: Department of Biomedical Sciences, College of Osteopathic Medicine, University of New England, Biddeford, ME 04005, USA. lcao@UNE.edu
authors.forename: Ling
authors.initials: L
authors.lastname: Cao
authors.forename: M Brady
authors.initials: MB
authors.lastname: Butler
authors.forename: Leonard
authors.initials: L
authors.lastname: Tan
authors.forename: Kyle S
authors.initials: KS
authors.lastname: Draleau
authors.forename: Woon Yuen
authors.initials: WY
authors.lastname: Koh
mesh_terms: D000818:Animals; D016207:Cytokines / Q000096:biosynthesis* / Q000235:genetics; D004195:Disease Models, Animal; D006967:Hypersensitivity / Q000276:immunology / Q000378:metabolism / Q000821:virology; D009052:Leukemia Virus, Murine / Q000276:immunology* / Q000302:isolation & purification; D007942:Leukemia, Experimental / Q000276:immunology / Q000378:metabolism / Q000821:virology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016183:Murine Acquired Immunodeficiency Syndrome / Q000276:immunology* / Q000378:metabolism*; D010523:Peripheral Nervous System Diseases / Q000276:immunology* / Q000378:metabolism / Q000821:virology*; D012333:RNA, Messenger / Q000096:biosynthesis; D012192:Retroviridae Infections / Q000276:immunology / Q000378:metabolism
chemical_list: D016207:Cytokines; D012333:RNA, Messenger