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.
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.
authors.affiliation: Institute of Clinical Infectious Diseases, Catholic University, Rome, Italy. andeluc@tin.it
authors.forename: A
authors.initials: A
authors.lastname: De Luca
authors.forename: M L
authors.initials: ML
authors.lastname: Giancola
authors.forename: A
authors.initials: A
authors.lastname: Cingolani
authors.forename: A
authors.initials: A
authors.lastname: Ammassari
authors.forename: R
authors.initials: R
authors.lastname: Murri
authors.forename: A
authors.initials: A
authors.lastname: Antinori
mesh_terms: D018791:CD4 Lymphocyte Count; D016022:Case-Control Studies; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018946:Chemokine CCL5 / Q000096:biosynthesis / Q000097:blood; D019742:Chemokines, CC / Q000096:biosynthesis / Q000097:blood*; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology* / Q000821:virology; D017320:HIV Protease Inhibitors / Q000627:therapeutic use*; D015497:HIV-1 / Q000302:isolation & purification; D006801:Humans; D066298:In Vitro Techniques; D019469:Indinavir / Q000627:therapeutic use; D007371:Interferon-gamma / Q000096:biosynthesis / Q000097:blood*; D007376:Interleukin-2 / Q000096:biosynthesis / Q000097:blood*; D007963:Leukocytes, Mononuclear / Q000276:immunology; D019402:Macrophage Inflammatory Proteins / Q000096:biosynthesis / Q000097:blood; D012367:RNA, Viral / Q000097:blood; D019438:Ritonavir / Q000627:therapeutic use
chemical_list: D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018946:Chemokine CCL5; D019742:Chemokines, CC; D017320:HIV Protease Inhibitors; D007376:Interleukin-2; D019402:Macrophage Inflammatory Proteins; D012367:RNA, Viral; D019469:Indinavir; D007371:Interferon-gamma; D019438:Ritonavir