De Luca A, Giancola M L, Cingolani A, Ammassari A, Murri R, Antinori A
Institute of Clinical Infectious Diseases, Catholic University, Rome, Italy.
AIDS Res Hum Retroviruses. 2000 Jun 10;16(9):835-43. doi: 10.1089/08892220050042774.
Cytokines and beta-chemokines play an important role in the complex interaction between HIV-1 and the immune system. We studied platelet-free plasma (PFP) levels and ex vivo production of cytokines and beta-chemokines at different HIV disease stages and the influence of potent protease inhibitor therapy on their production in late-stage patients. Mitogen-induced production of MIP-1alpha, MIP-1beta, and RANTES by PBMCs was higher in HIV-infected patients than in HIV-seronegative controls. Patients with late-stage HIV infection (CD4+ cells <50/microl) showed a higher production of MIP-1alpha and RANTES and lower plasma levels of IL-2 compared with HIV-positive patients at the intermediate stage (CD4+ cells >150/microl). Pretreatment RANTES production correlated negatively with CD4+ and CD8+ cell counts; also, MIP-1alpha production was inversely correlated with CD4+ cell counts. Among patients with a CD4+ cell count <50/microl, RANTES production before protease inhibitor treatment was inversely correlated with viral load. Late-stage patients with IL-2 production higher than 50 pg/ml before treatment showed a more impressive increase in CD4+ cell counts after protease inhibitor therapy. The production of MIP-1alpha, MIP-1beta, RANTES, and IFN-gamma was markedly reduced at 8 weeks and partially restored at 24 weeks after beginning protease inhibitor therapy. PFP levels of RANTES showed a concurrent decrease. Patients with more advanced HIV infection show a higher production of inflammatory cytokines, which is reduced by protease inhibitor therapy. Residual late-stage IL-2 producers may represent a subset of patients with a higher potential for immunologic reconstitution.
细胞因子和β趋化因子在HIV-1与免疫系统之间的复杂相互作用中发挥着重要作用。我们研究了不同HIV疾病阶段无血小板血浆（PFP）水平以及细胞因子和β趋化因子的体外产生情况，以及强效蛋白酶抑制剂疗法对晚期患者其产生的影响。与HIV血清阴性对照相比，HIV感染患者外周血单核细胞（PBMC）经丝裂原诱导产生的MIP-1α、MIP-1β和RANTES更高。与中期HIV阳性患者（CD4 +细胞>150/μl）相比，晚期HIV感染患者（CD4 +细胞<50/μl）表现出更高的MIP-1α和RANTES产生以及更低的IL-2血浆水平。治疗前RANTES产生与CD4 +和CD8 +细胞计数呈负相关；同样，MIP-1α产生与CD4 +细胞计数呈负相关。在CD4 +细胞计数<50/μl的患者中，蛋白酶抑制剂治疗前RANTES产生与病毒载量呈负相关。治疗前IL-2产生高于50 pg/ml的晚期患者在蛋白酶抑制剂治疗后CD4 +细胞计数增加更为显著。开始蛋白酶抑制剂治疗后8周，MIP-1α、MIP-1β、RANTES和IFN-γ的产生明显减少，24周时部分恢复。RANTES的PFP水平同时下降。HIV感染更严重的患者表现出更高的炎性细胞因子产生，蛋白酶抑制剂疗法可降低这种产生。残留的晚期IL-2产生者可能代表具有更高免疫重建潜力的患者亚组。
