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  • Title: Circulating levels and ex vivo production of beta-chemokines, interferon gamma, and interleukin 2 in advanced human immunodeficiency virus type 1 infection: the effect of protease inhibitor therapy.
    Author: De Luca A, Giancola ML, Cingolani A, Ammassari A, Murri R, Antinori A.
    Journal: AIDS Res Hum Retroviruses; 2000 Jun 10; 16(9):835-43. PubMed ID: 10875609.
    Abstract:
    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.
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