title: Effects of subcutaneous interleukin-2 therapy on CD4 subsets and in vitro cytokine production in HIV+ subjects.
abstract: HIV infection is characterized by the reduction of the CD4+, CD45RA+, CD26+, and CD28+ lymphocyte subsets and of the in vitro production of IL-2, IL-4, and interferon-gamma; on the contrary, chemokine production is usually increased. These abnormalities are only partially restored by antiretroviral chemotherapy. Therapy with interleukin-2 has been proposed to restore the functions of the immune system, but the mechanisms by which IL-2 exerts its activities are unknown. The aim of this study was to define the effects of rIL-2 administration on CD4+, CD45RA+, CD45R0+, and CD26+ lymphocytes and on the in vitro production of IL-2, IL-4, IL-10, IFN-gamma, RANTES, and sCD30 in HIV+ patients. 10 HIV+ patients with CD4 cell counts between 200 and 500 cells/mm3 were treated with six cycles of subcutaneous recombinant IL-2 administration, in combination with zidovudine and didanosine. This therapeutic regimen resulted in a remarkable increase in the number of CD4+ cells and in the prolonged reduction of the levels of viremia. CD45R01 cells were expanded during the first cycle of therapy, while CD45RA+/CD26+ cells predominated after the third cycle. At this time, the in vitro production of IL-2, IL-4, IFN-gamma, and sCD30 were significantly upregulated. These results demonstrate that rIL-2 in HIV+ patients induces the reconstitution of the CD4/CD45RA lymphocytes subtype. This expanded cell population recovered the ability to produce in vitro IL-2, IL-4, and IFN-gamma. These effects may be beneficial to HIV+ patients by improving their immune response to microorganisms or vaccines.
authors.affiliation: Department of Microbiology, Immunology, and Virology, Centro di Riferimento Oncologico, IRCCS, 33081 Aviano, Italy. pdepaoli@ets.it
authors.forename: P
authors.initials: P
authors.lastname: De Paoli
authors.forename: S
authors.initials: S
authors.lastname: Zanussi
authors.forename: C
authors.initials: C
authors.lastname: Simonelli
authors.forename: M T
authors.initials: MT
authors.lastname: Bortolin
authors.forename: M
authors.initials: M
authors.lastname: D'Andrea
authors.forename: C
authors.initials: C
authors.lastname: Crepaldi
authors.forename: R
authors.initials: R
authors.lastname: Talamini
authors.forename: M
authors.initials: M
authors.lastname: Comar
authors.forename: M
authors.initials: M
authors.lastname: Giacca
authors.forename: U
authors.initials: U
authors.lastname: Tirelli
mesh_terms: D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects*; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects; D002478:Cells, Cultured; D018946:Chemokine CCL5 / Q000096:biosynthesis; D016207:Cytokines / Q000096:biosynthesis*; D018819:Dipeptidyl Peptidase 4 / Q000276:immunology; D015658:HIV Infections / Q000097:blood / Q000276:immunology* / Q000628:therapy* / Q000821:virology; D006801:Humans; D007279:Injections, Subcutaneous; D007371:Interferon-gamma / Q000096:biosynthesis; D016753:Interleukin-10 / Q000096:biosynthesis; D007376:Interleukin-2 / Q000627:therapeutic use*; D015847:Interleukin-4 / Q000096:biosynthesis; D017730:Ki-1 Antigen / Q000096:biosynthesis; D017493:Leukocyte Common Antigens / Q000276:immunology; D011994:Recombinant Proteins / Q000627:therapeutic use; D014766:Viremia / Q000276:immunology / Q000628:therapy
chemical_list: D018946:Chemokine CCL5; D016207:Cytokines; D007376:Interleukin-2; D017730:Ki-1 Antigen; D011994:Recombinant Proteins; D016753:Interleukin-10; D015847:Interleukin-4; D007371:Interferon-gamma; D017493:Leukocyte Common Antigens; D018819:Dipeptidyl Peptidase 4