Effects of subcutaneous interleukin-2 therapy on CD4 subsets and in vitro cytokine production in HIV+ subjects.
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.
De Paoli
P
P
Department of Microbiology, Immunology, and Virology, Centro di Riferimento Oncologico, IRCCS, 33081 Aviano, Italy. pdepaoli@ets.it
Zanussi
S
S
Simonelli
C
C
Bortolin
M T
MT
D'Andrea
M
M
Crepaldi
C
C
Talamini
R
R
Comar
M
M
Giacca
M
M
Tirelli
U
U
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
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