Arango Juan-Carlos, Simmonds Peter, Brettle Ray P, Bell Jeanne E
School of Molecular and Clinical Medicine, Pathology (Neuropathology), University of Edinburgh, Edinburgh, Scotland, UK.
AIDS. 2004 Jan 1;18 Suppl 1:S69-74.
To investigate the pathological evidence for a possible interaction between drugs of abuse and HIV infection in terms of microglial responses in early and late HIV/AIDS, and to discuss the possible long-term consequences of microglial activation in chronic HIV infection.
This brain pathology study compared age and sex-matched control patients with HIV-negative intravenous drug users, and with HIV-positive drug users both in the presymptomatic stage and with AIDS. A further group of non-drug-using AIDS patients was included. All the AIDS patients had HIV encephalitis (HIVE) but no other significant HIV-associated brain pathology.
Microglia/macrophages were identified in the grey and white matter of the frontal and temporal lobes and the thalamus, using antibodies to CD68 and MHCII. Objective quantitation was used to compare subjects in the different groups.
AIDS patients showed a significant increase in activated microglia/macrophages in both the grey and white matter of all areas compared with non-AIDS patients. Drug users with HIVE tended to have more activated microglia than non-drug-using comparison groups, but this difference was not found in all brain areas studied.
Drug misuse appears to enhance the microglial activation resulting from HIV infection in some individuals. Other factors such as the severity of HIVE, or systemic immune factors, are also likely to affect the degree of microglial activation. The implications for drug-using patients who survive long term with HIV/AIDS are discussed, particularly in relation to premature neurodegeneration.
从早期和晚期HIV/AIDS患者小胶质细胞反应方面,研究药物滥用与HIV感染之间可能存在相互作用的病理证据,并探讨慢性HIV感染中小胶质细胞激活可能产生的长期后果。
这项脑病理学研究将年龄和性别匹配的对照组患者与HIV阴性静脉吸毒者、无症状期HIV阳性吸毒者以及艾滋病患者进行比较。还纳入了另一组非吸毒艾滋病患者。所有艾滋病患者均患有HIV脑炎(HIVE),但无其他明显的与HIV相关的脑部病变。
使用抗CD68和MHCII抗体,在额叶、颞叶和丘脑的灰质和白质中识别小胶质细胞/巨噬细胞。采用客观定量法比较不同组别的受试者。
与非艾滋病患者相比,艾滋病患者所有区域的灰质和白质中活化的小胶质细胞/巨噬细胞均显著增加。患有HIVE的吸毒者比非吸毒对照组的活化小胶质细胞往往更多,但并非在所有研究的脑区都发现这种差异。
药物滥用似乎会增强某些个体因HIV感染导致的小胶质细胞激活。其他因素,如HIVE的严重程度或全身免疫因素,也可能影响小胶质细胞激活的程度。文中讨论了长期存活的HIV/AIDS吸毒患者的相关影响,特别是与过早神经变性的关系。