Circulating levels and ex vivo production of β-chemokines, interferon γ, and interleukin 2 in advanced human immunodeficiency virus type 1 infection:: The effect of protease inhibitor therapy

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-1 alpha, MIP-1 beta, and RANTES by PBMCs was higher in HIV-infected patients than in HIV-seronegative controls. Patients with late-stage HIV infection (CD4(+) cells <50/mu l) showed a higher production of MIP-1 alpha and RANTES and lower plasma levels of IL-2 compared with HIV-positive patients at the intermediate stage (CD4(+) cells >150/mu l). Pretreatment RANTES production correlated negatively with CD4(+) and CD8(+) cell counts; also, MIP-la production was inversely correlated with CD4(+) cell counts. Among patients with a CD4(+) cell, count <50/mu l, 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-1 alpha, MIP-1 beta, 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.