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